39 results on '"van't Hooft F"'
Search Results
2. Genetic studies of body mass index yield new insights for obesity biology
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Locke, A, Kahali, B, Berndt, S, Justice, A, Pers, T, Day, F, Powell, C, Vedantam, S, Buchkovich, M, Yang, J, Croteau-Chonka, D, Esko, T, Fall, T, Ferreira, T, Gustafsson, S, Kutalik, Z, Luan, J, Magi, R, Randall, J, Winkler, T, Wood, A, Workalemahu, T, Faul, J, Smith, J, Zhao, J, Zhao, W, Chen, J, Fehrmann, R, Hedman, A, Karjalainen, J, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bolton, J, Bragg-Gresham, J, Buyske, S, Demirkan, A, Deng, G, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Goel, A, Gong, J, Jackson, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Leach, I, Medina-Gomez, C, Medland, S, Nalls, M, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Shungin, D, Stancakova, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, van der Laan, S, van Setten, J, Van Vliet-Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Isaacs, A, Albrecht, E, Arnlov, J, Arscott, G, Attwood, A, Bandinelli, S, Barrett, A, Bas, I, Bellis, C, Bennett, A, Berne, C, Blagieva, R, Bluher, M, Bohringer, S, Bonnycastle, L, Bottcher, Y, Boyd, H, Bruinenberg, M, Caspersen, I, Chen, Y, Clarke, R, Daw, E, de Craen, A, Delgado, G, Dimitriou, M, Doney, A, Eklund, N, Estrada, K, Eury, E, Folkersen, L, Fraser, R, Garcia, M, Geller, F, Giedraitis, V, Gigante, B, Go, A, Golay, A, Goodall, A, Gordon, S, Gorski, M, Grabe, H, Grallert, H, Grammer, T, Grassler, J, Gronberg, H, Groves, C, Gusto, G, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heard-Costa, N, Helmer, Q, Hengstenberg, C, Holmen, O, Hottenga, J, James, A, Jeff, J, Johansson, A, Jolley, J, Juliusdottir, T, Kinnunen, L, Koenig, W, Koskenvuo, M, Kratzer, W, Laitinen, J, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindstrom, J, Lo, K, Lobbens, S, Lorbeer, R, Lu, Y, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Mclachlan, S, Menni, C, Merger, S, Mihailov, E, Milani, L, Moayyeri, A, Monda, K, Morken, M, Mulas, A, Muller, G, Muller-Nurasyid, M, Musk, A, Nagaraja, R, Nothen, M, Nolte, I, Pilz, S, Rayner, N, Renstrom, F, Rettig, R, Ried, J, Ripke, S, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Scott, W, Seufferlein, T, Shi, J, Smith, A, Smolonska, J, Stanton, A, Steinthorsdottir, V, Stirrups, K, Stringham, H, Sundstrom, J, Swertz, M, Swift, A, Syvanen, A, Tan, S, Tayo, B, Thorand, B, Thorleifsson, G, Tyrer, J, Uh, H, Vandenput, L, Verhulst, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Warren, H, Waterworth, D, Weedon, M, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Brennan, E, Choi, M, Dastani, Z, Drong, A, Eriksson, P, Franco-Cereceda, A, Gadin, J, Gharavi, A, Goddard, M, Handsaker, R, Huang, J, Karpe, F, Kathiresan, S, Keildson, S, Kiryluk, K, Kubo, M, Lee, J, Liang, L, Lifton, R, Ma, B, Mccarroll, S, Mcknight, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Okada, Y, Perry, J, Dorajoo, R, Reinmaa, E, Salem, R, Sandholm, N, Scott, R, Stolk, L, Takahashi, A, Van't Hooft, F, Vinkhuyzen, A, Westra, H, Zheng, W, Zondervan, K, Heath, A, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Bovet, P, Campbell, H, Caulfield, M, Cesana, G, Chakravarti, A, Chasman, D, Chines, P, Collins, F, Crawford, D, Cupples, L, Cusi, D, Danesh, J, de Faire, U, Den Ruijter, H, Dominiczak, A, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Felix, S, Ferrannini, E, Ferrieres, J, Ford, I, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gejman, P, Gieger, C, Gottesman, O, Gudnason, V, Gyllensten, U, Hall, A, Harris, T, Hattersley, A, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Homuth, G, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Illig, T, Jacobs, K, Jarvelin, M, Jockel, K, Johansen, B, Jousilahti, P, Jukema, J, Jula, A, Kaprio, J, Kastelein, J, Keinanen-Kiukaanniemi, S, Kiemeney, L, Knekt, P, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Marchand, L, Lehtimaki, T, Lyssenko, V, Mannisto, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Moll, F, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Madden, P, Pasterkamp, G, Peden, J, Peters, A, Postma, D, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Rioux, J, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schunkert, H, Schwarz, P, Sever, P, Shuldiner, A, Sinisalo, J, Stolk, R, Strauch, K, Tonjes, A, Tregouet, D, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Volker, U, Waeber, G, Willemsen, G, Witteman, J, Zillikens, M, Adair, L, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bornstein, S, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hui, J, Hunter, D, Hveem, K, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, Marz, W, Melbye, M, Metspalu, A, Moebus, S, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Perusse, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sattar, N, Schadt, E, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Walker, M, Wallaschofski, H, Wareham, N, Watkins, H, Weir, D, Wichmann, H, Wilson, J, Zanen, P, Borecki, I, Deloukas, P, Fox, C, Heid, I, O'Connell, J, Strachan, D, Stefansson, K, van Duijn, C, Abecasis, G, Franke, L, Frayling, T, Mccarthy, M, Visscher, P, Scherag, A, Willer, C, Boehnke, M, Mohlke, K, Lindgren, C, Beckmann, J, Barroso, I, North, K, Ingelsson, E, Hirschhorn, J, Loos, R, Speliotes, E, Thompson, J, Goldstein, B, Konig, I, Cazier, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikainen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Claudi-Boehm, S, Cox, D, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schafer, A, Sivananthan, M, Song, C, Stewart, A, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Tsun-Po, Y, Basart, H, Brambilla, P, Cambien, F, Cupples, A, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kahonen, M, Kee, F, Kim, H, Klopp, N, Kuulasmaa, K, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Wallentin, L, Zimmermann, M, Nieminen, M, Sandhu, M, Pastinen, T, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Roberts, R, Pattaro, C, Kottgen, A, Garnaas, M, Boger, C, Fuchsberger, C, Olden, M, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Liu, C, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Lohman, K, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, Hu, F, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Doring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Ellinghaus, D, Nothlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Volzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Kramer, B, Portas, L, Buckley, B, Adam, M, Thun, G, Paulweber, B, Haun, M, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Vollenweider, P, Gasparini, P, Pirastu, M, Probst-Hensch, N, Kronenberg, F, Toniolo, D, Coresh, J, Schmidt, R, Siscovick, D, Kardia, S, Curhan, G, Franke, A, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, Arking, D, Franceschini, N, Egan, J, Hernandez, D, Townsend, R, Lumley, T, Psaty, B, Kestenbaum, B, Haritunians, T, Mooser, V, Florez, J, Meigs, J, Lu, X, Leak, T, Aasarod, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Kedenko, L, Coassin, S, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Dreisbach, A, Anderson, C, Guo, Q, Henders, A, Lambert, A, Lee, S, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Makinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkila, O, Hietala, K, Kyto, J, Lahermo, P, Lehto, M, Osterholm, A, Parkkonen, M, Pitkaniemi, J, Rosengard-Barlund, M, Saraheimo, M, Sarti, C, Soderlund, J, Soro-Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Waden, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc-Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Mollsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Freitag, D, Gurdasani, D, Heikkila, K, Johnson, T, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Teslovich, T, Van den Herik, E, Volcik, K, Wu, Y, Asiki, G, Been, L, Burnett, M, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Khaw, K, Kim, E, Komulainen, P, Lin, S, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Young, E, Bennett, F, Boomsma, D, Burnier, M, Feranil, A, Freimer, N, Hsiung, C, Kesaniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Meneton, P, Moilanen, L, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton-Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sober, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjogren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland-Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Brown, M, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Staessen, J, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Smith, G, Raffel, L, Yao, J, Schwartz, S, Ikram, M, W, L, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace-Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Wurtz, P, Ong, R, Dorr, M, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Guo, X, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, Palmer, L, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Alizadeh, B, de Boer, R, Boezen, H, Hillege, H, van der Klauw, M, Ormel, J, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Rasmussen-Torvik, L, Lecoeur, C, Johnson, P, Sennblad, B, Salo, P, Timpson, N, Evans, D, St Pourcain, B, Bielak, L, Horikoshi, M, Navarro, P, Raychaudhuri, S, Chen, H, Rybin, D, Willems, S, Song, K, An, P, Marullo, L, Jansen, H, Pankow, J, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Small, K, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Penninx, B, Toenjes, A, Peyser, P, Korner, A, Dupuis, J, Cucca, F, Balkau, B, Bouatia-Naji, N, Purcell, S, Musunuru, K, Ardissino, D, Mannucci, P, Anand, S, Engert, J, Morgan, T, Spertus, J, Stoll, M, Girelli, D, Mckeown, P, Patterson, C, Merlini, P, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Subirana, I, Sala, J, Ramos, R, Williams, G, Nathan, D, Macrae, C, Berglund, G, Asselta, R, Duga, S, Spreafico, M, Daly, M, Nemesh, J, Korn, J, Surti, A, Gianniny, L, Parkin, M, Burtt, N, Gabriel, S, Wright, B, Ball, S, Schunkert, I, Linsel-Nitschke, P, Lieb, W, Fischer, M, Grosshennig, A, Preuss, M, Scholz, M, Chen, Z, Wilensky, R, Matthai, W, Qasim, A, Hakonarson, H, Devaney, J, Pichard, A, Kent, K, Satler, L, Lindsay, J, Waksman, R, Knouff, C, Scheffold, T, Berger, K, Huge, A, Martinelli, N, Olivieri, O, Corrocher, R, Xie, C, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, Di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Yang, T, Higashio, J, Williams, R, Nato, A, Ambite, J, Deelman, E, Manolio, T, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown-Gentry, K, Thornton-Wells, T, Dumitrescu, L, Bush, W, Mitchell, S, Goodloe, R, Wilson, S, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Spencer, K, Pendergrass, S, Le Marchand, L, Park, L, Tiirikainen, M, Kolonel, L, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Anderson, G, Carlson, C, Prentice, R, Lacroix, A, Wu, C, Carty, C, Rosse, S, Young, A, Kocarnik, J, Lin, Y, Jackson, R, Duggan, D, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hankinson, S, Hass, M, Janssens, A, Karasik, D, Keyzer, J, Kiel, D, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Melzer, D, Newman, A, Pare, G, Peeters, P, Pop, V, Raikkonen, K, Salumets, A, Stacey, S, Starr, J, Stathopoulou, M, Styrkarsdottir, U, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Widen, E, Wijnands-Van Gent, C, Yerges-Armstrong, L, Zgaga, L, Zygmunt, M, Buring, J, 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E., Kahali B., Berndt S. I., Justice A. E., Pers T. H., Day F. R., Powell C., Vedantam S., Buchkovich M. L., Yang J., Croteau-Chonka D. C., Esko T., Fall T., Ferreira T., Gustafsson S., Kutalik Z., Luan J., Magi R., Randall J. C., Winkler T. W., Wood A. R., Workalemahu T., Faul J. D., Smith J. A., Zhao J. H., Zhao W., Chen J., Fehrmann R., Hedman A. K., Karjalainen J., Schmidt E. M., Absher D., Amin N., Anderson D., Beekman M., Bolton J. L., Bragg-Gresham J. L., Buyske S., Demirkan A., Deng G., Ehret G. B., Feenstra B., Feitosa M. F., Fischer K., Goel A., Gong J., Jackson A. U., Kanoni S., Kleber M. E., Kristiansson K., Lim U., Lotay V., Mangino M., Leach I. M., Medina-Gomez C., Medland S. E., Nalls M. A., Palmer C. D., Pasko D., Pechlivanis S., Peters M. J., Prokopenko I., Shungin D., Stancakova A., Strawbridge R. J., Sung Y. J., Tanaka T., Teumer A., Trompet S., van der Laan S. W., van Setten J., Van Vliet-Ostaptchouk J. 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E., Kahali B., Berndt S. I., Justice A. E., Pers T. H., Day F. R., Powell C., Vedantam S., Buchkovich M. L., Yang J., Croteau-Chonka D. C., Esko T., Fall T., Ferreira T., Gustafsson S., Kutalik Z., Luan J., Magi R., Randall J. C., Winkler T. W., Wood A. R., Workalemahu T., Faul J. D., Smith J. A., Zhao J. H., Zhao W., Chen J., Fehrmann R., Hedman A. K., Karjalainen J., Schmidt E. M., Absher D., Amin N., Anderson D., Beekman M., Bolton J. L., Bragg-Gresham J. L., Buyske S., Demirkan A., Deng G., Ehret G. B., Feenstra B., Feitosa M. F., Fischer K., Goel A., Gong J., Jackson A. U., Kanoni S., Kleber M. E., Kristiansson K., Lim U., Lotay V., Mangino M., Leach I. M., Medina-Gomez C., Medland S. E., Nalls M. A., Palmer C. D., Pasko D., Pechlivanis S., Peters M. J., Prokopenko I., Shungin D., Stancakova A., Strawbridge R. J., Sung Y. J., Tanaka T., Teumer A., Trompet S., van der Laan S. W., van Setten J., Van Vliet-Ostaptchouk J. V., Wang Z., Yengo L., Zhang W., Isaacs A., Albrecht E., Arnlov J., Arscott G. M., Attwood A. P., Bandinelli S., Barrett A., Bas I. N., Bellis C., Bennett A. J., Berne C., Blagieva R., Bluher M., Bohringer S., Bonnycastle L. L., Bottcher Y., Boyd H. A., Bruinenberg M., Caspersen I. H., Chen Y. I., Clarke R., Daw E. W., de Craen A. J. M., Delgado G., Dimitriou M., Doney A. S. F., Eklund N., Estrada K., Eury E., Folkersen L., Fraser R. M., Garcia M. E., Geller F., Giedraitis V., Gigante B., Go A. S., Golay A., Goodall A. H., Gordon S. D., Gorski M., Grabe H. J., Grallert H., Grammer T. B., Grassler J., Gronberg H., Groves C. J., Gusto G., Haessler J., Hall P., Haller T., Hallmans G., Hartman C. A., Hassinen M., Hayward C., Heard-Costa N. L., Helmer Q., Hengstenberg C., Holmen O., Hottenga J. J., James A. L., Jeff J. M., Johansson A., Jolley J., Juliusdottir T., Kinnunen L., Koenig W., Koskenvuo M., Kratzer W., Laitinen J., Lamina C., Leander K., Lee N. R., Lichtner P., Lind L., Lindstrom J., Lo K. S., Lobbens S., Lorbeer R., Lu Y., Mach F., Magnusson P. K. E., Mahajan A., McArdle W. L., McLachlan S., Menni C., Merger S., Mihailov E., Milani L., Moayyeri A., Monda K. L., Morken M. A., Mulas A., Muller G., Muller-Nurasyid M., Musk A. W., Nagaraja R., Nothen M. M., Nolte I. M., Pilz S., Rayner N. W., Renstrom F., Rettig R., Ried J. S., Ripke S., Robertson N. R., Rose L. M., Sanna S., Scharnagl H., Scholtens S., Schumacher F. R., Scott W. R., Seufferlein T., Shi J., Smith A. V., Smolonska J., Stanton A. V., Steinthorsdottir V., Stirrups K., Stringham H. M., Sundstrom J., Swertz M. A., Swift A. J., Syvanen A. C., Tan S. T., Tayo B. O., Thorand B., Thorleifsson G., Tyrer J. P., Uh H. W., Vandenput L., Verhulst F. C., Vermeulen S. H., Verweij N., Vonk J. M., Waite L. L., Warren H. R., Waterworth D., Weedon M. N., Wilkens L. R., Willenborg C., Wilsgaard T., Wojczynski M. K., Wong A., Wright A. F., Zhang Q., Brennan E. P., Choi M., Dastani Z., Drong A. W., Eriksson P., Franco-Cereceda A., Gadin J. R., Gharavi A. G., Goddard M. E., Handsaker R. E., Huang J., Karpe F., Kathiresan S., Keildson S., Kiryluk K., Kubo M., Lee J. Y., Liang L., Lifton R. P., Ma B., McCarroll S. A., McKnight A. J., Min J. L., Moffatt M. F., Montgomery G. W., Murabito J. M., Nicholson G., Nyholt D. R., Okada Y., Perry J. R. B., Dorajoo R., Reinmaa E., Salem R. M., Sandholm N., Scott R. A., Stolk L., Takahashi A., Van't Hooft F. M., Vinkhuyzen A. A. E., Westra H. J., Zheng W., Zondervan K. T., Heath A. C., Arveiler D., Bakker S. J. L., Beilby J., Bergman R. N., Blangero J., Bovet P., Campbell H., Caulfield M. J., Cesana G., Chakravarti A., Chasman D. I., Chines P. S., Collins F. S., Crawford D. C., Cupples L. A., Cusi D., Danesh J., de Faire U., Den Ruijter H. M., Dominiczak A. F., Erbel R., Erdmann J., Eriksson J. G., Farrall M., Felix S. B., Ferrannini E., Ferrieres J., Ford I., Forouhi N. G., Forrester T., Franco O. H., Gansevoort R. T., Gejman P. V., Gieger C., Gottesman O., Gudnason V., Gyllensten U., Hall A. S., Harris T. B., Hattersley A. T., Hicks A. A., Hindorff L. A., Hingorani A. D., Hofman A., Homuth G., Hovingh G. K., Humphries S. E., Hunt S. C., Hypponen E., Illig T., Jacobs K. B., Jarvelin M. R., Jockel K. H., Johansen B., Jousilahti P., Jukema J. W., Jula A. M., Kaprio J., Kastelein J. J. P., Keinanen-Kiukaanniemi S. M., Kiemeney L. A., Knekt P., Kooner J. S., Kooperberg C., Kovacs P., Kraja A. T., Kumari M., Kuusisto J., Lakka T. A., Langenberg C., Marchand L. L., Lehtimaki T., Lyssenko V., Mannisto S., Marette A., Matise T. C., McKenzie C. A., McKnight B., Moll F. L., Morris A. D., Morris A. P., Murray J. C., Nelis M., Ohlsson C., Oldehinkel A. J., Ong K. K., Madden P. A. F., Pasterkamp G., Peden J. F., Peters A., Postma D. S., Pramstaller P. P., Price J. F., Qi L., Raitakari O. T., Rankinen T., Rao D. C., Rice T. K., Ridker P. M., Rioux J. D., Ritchie M. D., Rudan I., Salomaa V., Samani N. J., Saramies J., Sarzynski M. A., Schunkert H., Schwarz P. E. H., Sever P., Shuldiner A. R., Sinisalo J., Stolk R. P., Strauch K., Tonjes A., Tregouet D. A., Tremblay A., Tremoli E., Virtamo J., Vohl M. C., Volker U., Waeber G., Willemsen G., Witteman J. C., Zillikens M. C., Adair L. S., Amouyel P., Asselbergs F. W., Assimes T. L., Bochud M., Boehm B. O., Boerwinkle E., Bornstein S. R., Bottinger E. P., Bouchard C., Cauchi S., Chambers J. C., Chanock S. J., Cooper R. S., de Bakker P. I. W., Dedoussis G., Ferrucci L., Franks P. W., Froguel P., Groop L. C., Haiman C. A., Hamsten A., Hui J., Hunter D. J., Hveem K., Kaplan R. C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N. G., Marz W., Melbye M., Metspalu A., Moebus S., Munroe P. B., Njolstad I., Oostra B. A., Palmer C. N. A., Pedersen N. L., Perola M., Perusse L., Peters U., Power C., Quertermous T., Rauramaa R., Rivadeneira F., Saaristo T. E., Saleheen D., Sattar N., Schadt E. E., Schlessinger D., Slagboom P. E., Snieder H., Spector T. D., Thorsteinsdottir U., Stumvoll M., Tuomilehto J., Uitterlinden A. G., Uusitupa M., van der Harst P., Walker M., Wallaschofski H., Wareham N. J., Watkins H., Weir D. R., Wichmann H. E., Wilson J. F., Zanen P., Borecki I. B., Deloukas P., Fox C. S., Heid I. M., O'connell J. R., Strachan D. P., Stefansson K., van Duijn C. M., Abecasis G. R., Franke L., Frayling T. M., McCarthy M. I., Visscher P. M., Scherag A., Willer C. J., Boehnke M., Mohlke K. L., Lindgren C. M., Beckmann J. S., Barroso I., North K. E., Ingelsson E., Hirschhorn J. N., Loos R. J. F., Speliotes E. K., Thompson J. R., Goldstein B. A., Konig I. R., Cazier J. B., Grundberg E., Havulinna A. S., Ho W. K., Hopewell J. C., Eriksson N., Lundmark P., Lyytikainen L. P., Rafelt S., Tikkanen E., Van Zuydam N., Voight B. F., Ziegler A., Altshuler D., Balmforth A. J., Braund P. S., Burgdorf C., Claudi-Boehm S., Cox D., Do R., Doney A. S., El Mokhtari N., Fontanillas P., Hager J., Han B. G., Hunt S. E., Kang H. M., Kessler T., Knowles J. W., Kolovou G., Langford C., Lokki M. L., Lundmark A., Meisinger C., Melander O., Maouche S., Nikus K., Rasheed A., Rosinger S., Rubin D., Rumpf M. P., Schafer A., Sivananthan M., Song C., Stewart A. F., Thorgeirsson G., van der Schoot C. E., Wagner P. J., Wells G. A., Wild P. S., Tsun-Po Y., Basart H. V., Brambilla P., Cambien F., Cupples A. L., Dehghan A., Diemert P., Epstein S. E., Evans A., Ferrario M., Gauguier D., Hazen S. L., Holm H., Iribarren C., Jang Y., Kahonen M., Kee F., Kim H. S., Klopp N., Kuulasmaa K., Laaksonen R., Ouwehand W. H., Parish S., Park J. E., Rader D. J., Shah S. H., Stark K., Wallentin L., Zimmermann M. E., Nieminen M. S., Sandhu M. S., Pastinen T., Zalloua P. A., Siegbahn A., Schreiber S., Ripatti S., Blankenberg S. S., O'donnell C. J., Reilly M., Collins R., Roberts R., Pattaro C., Kottgen A., Garnaas M., Boger C. A., Fuchsberger C., Olden M., Chen M. H., Tin A., Taliun D., Li M., Gao X., Yang Q., Hundertmark C., Foster M. C., O'seaghdha C. M., Glazer N. L., Liu C. T., Struchalin M., Li G., Johnson A. D., Gierman H. J., Hwang S. J., Atkinson E. J., Lohman K. K., Cornelis M. C., Chouraki V., Holliday E. G., Sorice R., Deshmukh H., Ulivi S., Chu A. Y., Murgia F., Imboden M., Kollerits B., Pistis G., Launer L. J., Aspelund T., Eiriksdottir G., Mitchell B. D., Schmidt H., Cavalieri M., Rao M., Hu F. B., de Andrade M., Turner S. T., Ding J., Andrews J. S., Freedman B. I., Doring A., Kolcic I., Zemunik T., Boban M., Minelli C., Wheeler H. E., Igl W., Zaboli G., Wild S. H., Ellinghaus D., Nothlings U., Jacobs G., Biffar R., Endlich K., Ernst F., Kroemer H. K., Nauck M., Stracke S., Volzke H., Aulchenko Y., Polasek O., Hastie N. D., Vitart V., Helmer C., Wang J. J., Ruggiero D., Bergmann S., Viikari J., Nikopensius T., Province M. A., Ketkar S., Colhoun H. M., Doney A., Robino A., Giulianini F., Kramer B. K., Portas L., Buckley B. M., Adam M., Thun G. A., Paulweber B., Haun M., Sala C., Metzger M., Mitchell P., Ciullo M., Kim S. K., Vollenweider P., Palmer C., Gasparini P., Pirastu M., Probst-Hensch N. M., Kronenberg F., Toniolo D., Coresh J., Schmidt R., Siscovick D. S., Kardia S. L., Curhan G., Franke A., Parsa A., Goessling W., Kao W. H., de Boer I. H., Peralta C. A., Akylbekova E., Kramer H., Arking D. E., Franceschini N., Egan J., Hernandez D. G., Townsend R. R., Lumley T., Psaty B. M., Kestenbaum B., Haritunians T., Mooser V., Florez J. C., Meigs J. B., Lu X., Leak T. S., Aasarod K., Skorpen F., Baumert J., Devuyst O., Mychaleckyj J. C., Kedenko L., Coassin S., Hallan S., Navis G., Shlipak M. G., Bull S. B., Paterson A. D., Rotter J. I., Dreisbach A. W., Anderson C. A., Guo Q., Henders A., Lambert A., Lee S. H., Kraft P., Kennedy S. H., Macgregor S., Missmer S. A., Painter J. N., Roseman F., Treloar S. A., Wallace L., Forsblom C., Isakova T., McKay G. J., Williams W. W., Sadlier D. M., Makinen V. P., Swan E. J., Boright A. P., Ahlqvist E., Keller B. J., Huang H., Ahola A., Fagerholm E., Gordin D., Harjutsalo V., He B., Heikkila O., Hietala K., Kyto J., Lahermo P., Lehto M., Osterholm A. M., Parkkonen M., Pitkaniemi J., Rosengard-Barlund M., Saraheimo M., Sarti C., Soderlund J., Soro-Paavonen A., Syreeni A., Thorn L. M., Tikkanen H., Tolonen N., Tryggvason K., Waden J., Gill G. V., Prior S., Guiducci C., Mirel D. B., Taylor A., Hosseini M., Parving H. H., Rossing P., Tarnow L., Ladenvall C., Alhenc-Gelas F., Lefebvre P., Rigalleau V., Roussel R., Maestroni A., Maestroni S., Falhammar H., Gu T., Mollsten A., Cimponeriu D., Mihai I., Mota M., Mota E., Serafinceanu C., Stavarachi M., Hanson R. L., Nelson R. G., Kretzler M., Panduru N. M., Gu H. F., Brismar K., Zerbini G., Hadjadj S., Marre M., Lajer M., Waggott D., Savage D. A., Bain S. C., Martin F., Godson C., Groop P. H., Maxwell A. P., Sengupta S., Peloso G. M., Ganna A., Mora S., Chang H. Y., Den Hertog H. M., Donnelly L. A., Freitag D. F., Gurdasani D., Heikkila K., Johnson T., Kaakinen M., Kettunen J., Li X., Montasser M. E., Petersen A. K., Saxena R., Service S. K., Sidore C., Surakka I., Teslovich T. M., Van den Herik E. G., Volcik K. A., Wu Y., Asiki G., Been L. F., Burnett M. S., Elliott P., Eyjolfsson G. I., Goodarzi M. O., Gravito M. L., Hartikainen A. L., Hung Y. J., Jones M. R., Kaleebu P., Khaw K. T., Kim E., Komulainen P., Lin S. Y., Narisu N., Nieminen T. V., Nsubuga R. N., Olafsson I., Palotie A., Papamarkou T., Pomilla C., Pouta A., Ruokonen A., Seeley J., Silander K., Tiret L., van Pelt L., Wainwright N., Wijmenga C., Young E. H., Bennett F., Boomsma D. I., Burnier M., Chen Y. D., Feranil A. B., Freimer N. B., Hsiung C. A., Kesaniemi A., Koudstaal P. J., Krauss R. M., Kyvik K. O., Meneton P., Moilanen L., Sanghera D. K., Sheu W. H., Whitfield J. B., Wolffenbuttel B. H., Ordovas J. M., Rich S. S., Johnson A., Johnson L., Larson M., Levy D., Newton-Cheh C., O'reilly P., Palmas W., Rice K., Smith A., Snider H., Tobin M., Verwoert G., Rice K. M., Verwoert G. C., Pihur V., Heath S., Sober S., Arora P., Zhang F., Lucas G., Milaneschi Y., Parker A. N., Fava C., Fox E. R., Go M. J., Sjogren M., Vinay D., Alexander M., Tabara Y., Shaw-Hawkins S., Whincup P. H., Shi G., Seielstad M., Sim X., Nguyen K. D., Matullo G., Gaunt T. R., Onland-Moret N. C., Cooper M. N., Platou C. G., Org E., Hardy R., Dahgam S., Palmen J., Kuznetsova T., Uiterwaal C. S., Adeyemo A., Ludwig B., Tomaszewski M., Tzoulaki I., Palmer N. D., Chang Y. P., Steinle N. I., Grobbee D. E., Morrison A. C., Najjar S., Hadley D., Brown M. J., Connell J. M., Day I. N., Lawlor D. A., Lawrence R. W., Ongen H., Li Y., Young J. H., Bis J. C., Bolton J. A., Chaturvedi N., Islam M., Jafar T. H., Kulkarni S. R., Howard P., Guarrera S., Ricceri F., Emilsson V., Plump A., Weder A. B., Sun Y. V., Scott L. J., Peltonen L., Vartiainen E., Brand S. M., Staessen J. A., Wang T. J., Burton P. R., Artigas M. S., Dong Y., Wang X., Zhu H., Rudock M. E., Heckbert S. R., Smith N. L., Wiggins K. L., Doumatey A., Shriner D., Veldre G., Viigimaa M., Kinra S., Prabhakaran D., Tripathy V., Langefeld C. D., Rosengren A., Thelle D. S., Corsi A. M., Singleton A., Hilton G., Salako T., Iwai N., Kita Y., Ogihara T., Ohkubo T., Okamura T., Ueshima H., Umemura S., Eyheramendy S., Meitinger T., Cho Y. S., Kim H. L., Scott J., Sehmi J. S., Hedblad B., Nilsson P., Smith G. D., Raffel L. J., Yao J., Schwartz S. M., Ikram M., W L., Mosley T. H., Seshadri S., Shrine N. R., Wain L. V., Zitting P., Cooper J. A., van Gilst W. H., Janipalli C. S., Mani K., Yajnik C. S., Mattace-Raso F. U., Lakatta E. G., Orru M., Scuteri A., Ala-Korpela M., Kangas A. J., Soininen P., Tukiainen T., Wurtz P., Ong R. T., Dorr M., Galan P., Hercberg S., Lathrop M., Zelenika D., Zhai G., Meschia J. F., Sharma P., Terzic J., Kumar M., Denniff M., Zukowska-Szczechowska E., Wagenknecht L. E., Fowkes F., Charchar F. J., Guo X., Rotimi C., Bots M. L., Brand E., Talmud P. J., Nyberg F., Laan M., Palmer L. J., van der Schouw Y. T., Casas J. P., Vineis P., Ganesh S. K., Wong T. Y., Tai E. S., Morris R. W., Marmot M. G., Miki T., Chandak G. R., Zhu X., Elosua R., Soranzo N., Sijbrands E. J., Uda M., Vasan R. S., Alizadeh B. Z., de Boer R. A., Boezen H. M., Hillege H. L., van der Klauw M. M., Ormel J., Rosmalen J. G., Slaets J. P., Lagou V., Welch R. P., Wheeler E., Rehnberg E., Rasmussen-Torvik L. J., Lecoeur C., Johnson P. C., Sennblad B., Salo P., Timpson N. J., Evans D. M., St Pourcain B., Bielak L. F., Horikoshi M., Navarro P., Raychaudhuri S., Chen H., Rybin D., Willems S. M., Song K., An P., Marullo L., Jansen H., Pankow J. S., Edkins S., Varga T. V., Oksa H., Antonella M., Kong A., Herder C., Antti J., Small K., Miljkovic I., Atalay M., Kiess W., Smit J. H., Campbell S., Fowkes G. R., Rathmann W., Maerz W., Watanabe R. M., de Geus E. J., Penninx B. W., Toenjes A., Peyser P. A., Korner A., Dupuis J., Cucca F., Balkau B., Bouatia-Naji N., Purcell S., Musunuru K., Ardissino D., Mannucci P. M., Anand S., Engert J. C., Morgan T., Spertus J. A., Stoll M., Girelli D., McKeown P. P., Patterson C. C., Merlini P. A., Berzuini C., Bernardinelli L., Peyvandi F., Tubaro M., Celli P., Fetiveau R., Marziliano N., Casari G., Galli M., Ribichini F., Rossi M., Bernardi F., Zonzin P., Piazza A., Yee J., Friedlander Y., Marrugat J., Subirana I., Sala J., Ramos R., Williams G., Nathan D. M., Macrae C. A., Berglund G., Asselta R., Duga S., Spreafico M., Daly M. J., Nemesh J., Korn J. M., Surti A., Gianniny L., Parkin M., Burtt N., Gabriel S. B., Wright B. J., Ball S. G., Schunkert I., Linsel-Nitschke P., Lieb W., Fischer M., Grosshennig A., Preuss M., Scholz M., Chen Z., Wilensky R., Matthai W., Qasim A., Hakonarson H. H., Devaney J., Pichard A. D., Kent K. M., Satler L., Lindsay J. M., Waksman R., Knouff C. W., Scheffold T., Berger K., Huge A., Martinelli N., Olivieri O., Corrocher R., Xie C., Ahmadi K. R., Ainali C., Bataille V., Bell J. T., Buil A., Dermitzakis E. T., Dimas A. S., Durbin R., Glass D., Hassanali N., Ingle C., Knowles D., Krestyaninova M., Lowe C. E., Meduri E., Di Meglio P., Montgomery S. B., Nestle F. O., Nica A. C., Nisbet J., O'rahilly S., Parts L., Potter S., Sekowska M., Shin S. Y., Surdulescu G., Travers M. E., Tsaprouni L., Tsoka S., Wilk A., Yang T. P., Higashio J., Williams R., Nato A., Ambite J. L., Deelman E., Manolio T., Heiss G., Taylor K., Avery C., Graff M., Lin D., Quibrera M., Cochran B., Kao L., Umans J., Cole S., Maccluer J., Person S., Gross M., Fornage M., Durda P., Jenny N., Patsy B., Arnold A., Buzkova P., Haines J., Murdock D., Glenn K., Brown-Gentry K., Thornton-Wells T., Dumitrescu L., Bush W. S., Mitchell S. L., Goodloe R., Wilson S., Boston J., Malinowski J., Restrepo N., Oetjens M., Fowke J., Spencer K., Pendergrass S., Le Marchand L., Park L., Tiirikainen M., Kolonel L., Cheng I., Wang H., Shohet R., Stram D., Henderson B., Monroe K., Anderson G., Carlson C., Prentice R., Lacroix A., Wu C., Carty C., Rosse S., Young A., Kocarnik J., Lin Y., Jackson R., Duggan D., Kuller L., He C., Sulem P., Barbalic M., Broer L., Byrne E. M., Gudbjartsson D. F., McArdle P. F., Porcu E., van Wingerden S. W., Zhuang W. V., Lauc L. B., Broekmans F. J., Burri A., Chen C., Corre T., Coviello A. D., D'adamo P., Davies G., Deary I. J., Ebrahim S., Fauser B. C., Ferreli L., Folsom A. R., Hankinson S. E., Hass M., Janssens A. C., Karasik D., Keyzer J., Kiel D. P., Lahti J., Lai S., Laisk T., Laven J. S., Liu J., Lopez L. M., Louwers Y. V., Marongiu M., Klaric I. M., Masciullo C., Melzer D., Newman A. B., Pare G., Peeters P. H., Pop V. J., Raikkonen K., Salumets A., Stacey S. N., Starr J. M., Stathopoulou M. G., Styrkarsdottir U., Tenesa A., Tryggvadottir L., Tsui K., van Dam R. M., van Gils C. H., van Nierop P., Vink J. M., Voorhuis M., Widen E., Wijnands-Van Gent C. J., Yerges-Armstrong L. M., Zgaga L., Zygmunt M., Buring J. E., Crisponi L., Demerath E. W., Streeten E. A., Murray A., Visser J. A., Lunetta K. L., Elks C. E., Cousminer D. L., Koller D. L., Lin P., Smith E. N., Warrington N. M., Alavere H., Berenson G. S., Blackburn H., Busonero F., Chen W., Couper D., Easton D. F., Eriksson J., Foroud T., Kilpelainen T. O., Li S., Murray S. S., Ness A. R., Northstone K., Peacock M., Pennell C. E., Pharoah P., Rafnar T., Rice J. P., Ring S. M., Schork N. J., Segre A. V., Sovio U., Srinivasan S. R., Tammesoo M. L., van Meurs J. B., Young L., Bierut L. J., and Econs M. J.
- Abstract
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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- 2015
3. HDL Subfractions, HDL Receptors and HDL Turnover
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van Tol, A., van’t Hooft, F. M., van Gent, T., Dallinga-Thie, G. M., Malmendier, C. L., editor, and Alaupovic, P., editor
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- 1987
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4. Large-scale gene-centric analysis identifies novel variants for coronary artery disease
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Butterworth, As, Braund, Ps, Farrall, M, Hardwick, Rj, Saleheen, D, Peden, Jf, Soranzo, N, Chambers, Jc, Sivapalaratnam, S, Kleber, Me, Keating, B, Qasim, A, Klopp, N, Erdmann, J, Assimes, Tl, Ball, Sg, Balmforth, Aj, Barnes, Ta, Basart, H, Baumert, J, Bezzina, Cr, Boerwinkle, E, Boehm, Bo, Brocheton, J, Bugert, P, Cambien, F, Clarke, R, Codd, V, Collins, R, Couper, D, Cupples, La, de Jong JS, Diemert, P, Ejebe, K, Elbers, Cc, Elliott, P, Fornage, M, Franzosi, Mg, Frossard, P, Garner, S, Goel, A, Goodall, Ah, Hengstenberg, C, Hunt, Se, Kastelein, Jj, Klungel, Oh, Klüter, H, Koch, K, König, Ir, Kooner, As, Laaksonen, R, Lathrop, M, Li, M, Liu, K, Mcpherson, R, Musameh, Md, Musani, S, Nelson, Cp, O'Donnell, Cj, Ongen, H, Papanicolaou, G, Peters, A, Peters, Bj, Potter, S, Psaty, Bm, Qu, L, Rader, Dj, Rasheed, A, Rice, C, Scott, J, Seedorf, U, Sehmi, Js, Sotoodehnia, N, Stark, K, Stephens, J, van der Schoot CE, van der Schouw YT, Thorsteinsdottir, U, Tomaszewski, M, van der Harst, P, Vasan, Rs, Wilde, Aa, Willenborg, C, Winkelmann, Br, Zaidi, M, Zhang, W, Ziegler, A, de Bakker PI, Koenig, W, Mätz, W, Trip, Md, Reilly, Mp, Kathiresan, S, Schunkert, H, Hamsten, A, Hall, As, Kooner, Js, Thompson, Sg, Thompson, Jr, Deloukas, P, Ouwehand, Wh, Watkins, H, Danesh, J, Samani, Nj, Barnes, T, Rafelt, S, Bruinsma, N, Dekker, Lr, Henriques, Jp, Koch, Kt, de Winter RJ, Alings, M, Allaart, Cf, Gorgels, Ap, Verheugt, Fw, Mueller, M, Meisinger, C, Derohannessian, S, Mehta, Nn, Ferguson, J, Hakonarson, H, Matthai, W, Wilensky, R, Hopewell, Jc, Parish, S, Linksted, P, Notman, J, Gonzalez, H, Young, A, Ostley, T, Munday, A, Goodwin, N, Verdon, V, Shah, S, Cobb, L, Edwards, C, Mathews, C, Gunter, R, Benham, J, Davies, C, Cobb, M, Crowther, J, Richards, A, Silver, M, Tochlin, S, Mozley, S, Clark, S, Radley, M, Kourellias, K, Silveira, A, Söderholm, B, Olsson, P, Barlera, S, Tognoni, G, Rust, S, Assmann, G, Heath, S, Zelenika, D, Gut, I, Green, F, Peden, J, Aly, A, Anner, K, Björklund, K, Blomgren, G, Cederschiöld, B, Danell Toverud, K, Eriksson, P, Grundstedt, U, Heinonen, M, Hellénius, Ml, van't Hooft, F, Husman, K, Lagercrantz, J, Larsson, A, Larsson, M, Mossfeldt, M, Mälarstig, A, Olsson, G, Sabater Lleal, M, Sennblad, B, Strawbridge, R, Öhrvik, J, Zaman, Ks, Mallick, Nh, Azhar, M, Samad, A, Ishaq, M, Shah, N, Samuel, M, Reilly, M, Holm, H, Preuss, M, Stewart, Af, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, S, Andersen, K, Anderson, Jl, Ardissino, D, Becker, Lc, Becker, Dm, Berger, K, Bis, Jc, Boekholdt, Sm, Brown, Mj, Burnett, Ms, Buysschaert, I, Carlquist, Jf, Chen, L, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, J, Do, R, Doering, A, El Mokhtari NE, Ellis, Sg, Elosua, R, Engert, Jc, Epstein, S, de Faire, U, Fischer, M, Folsom, Ar, Freyer, J, Gigante, B, Girelli, D, Gretarsdottir, S, Gudnason, V, Gulcher, Jr, Tennstedt, S, Halperin, E, Hammond, N, Hazen, Sl, Hofman, A, Horne, Bd, Illig, T, Iribarren, C, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kaplan, Lm, Khaw, Kt, Knowles, Jw, Kolovou, G, Kong, A, Lambrechts, D, Leander, K, Lieb, W, Lettre, G, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meitinger, T, Melander, O, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Musunuru, K, Nahrstaedt, J, Nöthen, Mm, Olivieri, Oliviero, Peyvandi, F, Patel, Rs, Patterson, Cc, Quyyumi, Aa, Rallidis, Ls, Roosendaal, Fr, Rubin, D, Salomaa, V, Sampietro, Ml, Sandhu, Ms, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, Sm, Siscovick, Ds, Sivananthan, M, Smith, Av, Smith, Tb, Snoep, Jd, Spertus, Ja, Stefansson, K, Stirrups, K, Stoll, M, Tang, Wh, Thorgeirsson, G, Thorleifsson, G, Uitterlinden, Ag, van Rij AM, Voight, Bf, Wareham, Nj, Awells, G, Wichmann, He, Witteman, Jc, Wright, Bj, Ye, S, Quertermous, T, März, W, Blankenberg, S, Roberts, R, Onland Moret NC, van Setten, J, Verschuren, Wm, Boer, Jm, Wijmenga, C, Hofker, Mh, Maitland van der Zee AH, de Boer, A, Grobbee, De, Attwood, T, Belz, S, Braund, P, Cooper, J, Crisp Hihn, A, Foad, N, Gracey, J, Gray, E, Gwilliams, R, Heimerl, S, Jolley, J, Krishnan, U, Lloyd Jones, H, Lugauer, I, Lundmark, P, Moore, Js, Muir, D, Murray, E, Neudert, J, Niblett, D, O'Leary, K, Pollard, H, Rankin, A, Rice, Cm, Sager, H, Sambrook, J, Schmitz, G, Scholz, M, Schroeder, L, Syvannen, Ac, Wallace, C., Cardiologie, RS: CAPHRI School for Public Health and Primary Care, Vascular Medicine, Other departments, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Landsteiner Laboratory, Clinical Haematology, Pulmonology, and Medical Research Council (MRC)
- Subjects
Male ,Cancer Research ,Candidate gene ,Epidemiology ,Genome-wide association study ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Cardiovascular ,0302 clinical medicine ,GENETICS & HEREDITY ,Genetics (clinical) ,Genetics ,0303 health sciences ,Cardiovascular diseases [NCEBP 14] ,Middle Aged ,3. Good health ,CYP17A1 ,Genetic Epidemiology ,Genome-wide association ,Myocardial-infarction ,Susceptibility loci ,Risk ,Atherosclerosis ,Metanalysis ,Lipoprotein ,Medicine ,Female ,Life Sciences & Biomedicine ,Research Article ,Asian Continental Ancestry Group ,Adult ,SUSCEPTIBILITY LOCI ,lcsh:QH426-470 ,European Continental Ancestry Group ,Biology ,Polymorphism, Single Nucleotide ,coronary artery disease ,genetics ,White People ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Asian People ,Genetic variation ,Humans ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,Allele ,Molecular Biology ,Gene ,METAANALYSIS ,Ecology, Evolution, Behavior and Systematics ,Genetic Association Studies ,Cardiovascular Disease Epidemiology ,Alleles ,030304 developmental biology ,Aged ,0604 Genetics ,Science & Technology ,Case-control study ,Genetic Variation ,Human Genetics ,Odds ratio ,large-scale gene analysis ,lcsh:Genetics ,LIPOPROTEIN ,MYOCARDIAL-INFARCTION ,ATHEROSCLEROSIS ,Case-Control Studies ,Genetics of Disease ,IBC 50K CAD Consortium ,Developmental Biology ,Genome-Wide Association Study - Abstract
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p, Author Summary Coronary artery disease (CAD) has a strong genetic basis that remains poorly characterised. Using a custom-designed array, we tested the association with CAD of almost 50,000 common and low frequency variants in ∼2,000 genes of known or suspected cardiovascular relevance. We genotyped the array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin) and attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. We report the novel association of variants in or near four genes with CAD and in additional studies identify potential mechanisms by which some of these novel variants affect CAD risk. Interestingly, we found that these variants, as well as the majority of previously reported CAD variants, have similar associations in Europeans and South Asians. Contrary to prior expectations, many previously suggested candidate genes did not show evidence of any effect on CAD risk, and neither did we identify any novel low frequency alleles with strong effects amongst the genes tested. Discovery of novel genes associated with heart disease may help to further understand the aetiology of cardiovascular disease and identify new targets for therapeutic interventions.
- Published
- 2016
5. Common polymorphisms in the factor VII gene locus influence the basal and postprandial plasma concentrations of activated factor VII
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Silveira, A, Nastase-Mannila, M, Karpe, F, Boquist, S, van't Hooft, F, Ehrenborg, E, and Hamsten, A
- Published
- 1999
6. PO6-176 HUMAN EVIDENCE FOR THE INVOLVEMENT OF INSIG-2 IN THE ADIPOSE TISSUE METABOLISM
- Author
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Krapivner, S., primary, Popov, S., additional, Chernogubova, E., additional, Hellenius, M-L., additional, Fisher, R., additional, Hamsten, A., additional, and van't Hooft, F., additional
- Published
- 2007
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7. Unique patient with cerebrotendinous xanthomatosis. Evidence for presence of a defect in a gene that is not identical to sterol 27‐hydroxylase
- Author
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Hansson, M., primary, Olin, M., additional, Floren, C.‐H., additional, Von Bahr, S., additional, Van't Hooft, F., additional, Meaney, S., additional, Eggertsen, G., additional, and Björkhem, I., additional
- Published
- 2007
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8. A Common Functional Polymorphism (C->A Substitution at Position -863) in the Promoter Region of the Tumour Necrosis Factor- (TNF- ) Gene Associated With Reduced Circulating Levels of TNF-
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Skoog, T., primary, van't Hooft, F. M., additional, Kallin, B., additional, Jovinge, S., additional, Boquist, S., additional, Nilsson, J., additional, Eriksson, P., additional, and Hamsten, A., additional
- Published
- 1999
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9. Potential of 99mTc-LDLs labeled by two different methods for scintigraphic detection of experimental atherosclerosis in rabbits.
- Author
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Atsma, D E, primary, Feitsma, R I, additional, Camps, J, additional, van't Hooft, F M, additional, van der Wall, E E, additional, Nieuwenhuizen, W, additional, and Pauwels, E K, additional
- Published
- 1993
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10. Relapsing polychondritis mimicking rheumatoid arthritis.
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Schlapbach, P, Gerber, N J, Ramser, P, and van't Hooft, F M
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RHEUMATOID arthritis diagnosis ,CARTILAGE diseases ,DIFFERENTIAL diagnosis - Abstract
A woman with relapsing polychondritis presented with progressive and deforming polyarthritis (but always negative for rheumatoid factor) 14 years before the appearance of typical clinical and histological changes of nasal and auricular cartilage destruction. [ABSTRACT FROM PUBLISHER]
- Published
- 1988
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11. Metabolism of apolipoprotein E in plasma high density lipoproteins from normal and cholesterol-fed rats.
- Author
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van't Hooft, F and Havel, R J
- Abstract
High density lipoproteins of rat blood plasma were labeled in vitro with radioiodinated apolipoprotein E and biologically with [3H]cholesteryl esters. These two components, present in high density lipoproteins separated from serum of normal or cholesterol-fed rats by molecular sieve chromatography, were removed slowly from perfused livers and the labeled apolipoprotein E was also removed slowly from the blood of intact rats. However, when labeled serum was subjected to ultracentrifugation at a density of 1.21 g/ml before the floating apolipoprotein E-labeled high density lipoproteins were separated by chromatography, the labeled protein was rapidly removed from the blood of intact rats by uptake into the liver. About one-half of the labeled apolipoprotein E associated with high density lipoproteins was dissociated during ultracentrifugation, but most of it reassociated with the these lipoproteins when the floating lipoproteins were remixed with the sedimented serum proteins. The apolipoprotein E in such reassociated high density lipoproteins was removed from the blood of intact rats at the slow rate observed when the high density lipoproteins were separated chromatographically from whole serum. About 90% of the labeled apolipoprotein E in uncentrifuged or centrifuged high density lipoproteins was shown by affinity chromatography to be associated with particles containing apolipoprotein A-I. Rapid hepatic uptake of apolipoprotein E in centrifuged high density lipoproteins may result from an altered conformation of the apolipoprotein E on the particle surface.
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- 1982
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12. The sites of degradation of rat high-density-lipoprotein apolipoprotein E specifically labelled with O-(4-diazo-3-[125I]iodobenzoyl)sucrose
- Author
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Van't Hooft, F M and Van Tol, A
- Abstract
O-(4-Diazo-3-[125I]iodobenzoyl)sucrose ([125I]DIBS), a novel labelling compound specifically designed to study the catabolic sites of serum proteins [De Jong, Bouma, & Gruber (1981) Biochem. J. 198, 45-51], was applied to study the tissue sites of degradation of serum lipoproteins. [125I]DIBS-labelled apolipoproteins (apo) E and A-I, added in tracer amounts to rat serum, associate with high-density lipoproteins (HDL) just like conventionally iodinated apo E and A-I. No difference is observed between the serum decays of chromatographically isolated [125I]DIBS-labelled and conventionally iodinated HDL labelled specifically in either apo E or apo A-I. When these specifically labelled HDLs are injected into fasted rats, a substantial [125I]DIBS-dependent 125I accumulation occurs in the kidneys and in the liver. No [125I]DIBS-dependent accumulation is observed in the kidneys after injection of labelled asialofetuin or human low-density lipoprotein. It is concluded that the kidneys and the liver are important sites of catabolism of rat HDL apo E and A-I.
- Published
- 1985
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13. Apolipoprotein B (B-48) of rat chylomicrons is not a precursor of the apolipoprotein of low density lipoproteins.
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Van't Hooft, F M, Hardman, D A, Kane, J P, and Havel, R J
- Abstract
We have found that, in chylomicrons from intestinal lymph fistulas in the rat, the sole molecular species of apolipoprotein B (apo B) is B-48. This protein is analogous to the B-48 apoprotein of human chylomicrons. In contrast, preparations of chylomicrons from blood serum are known to contain species of B apolipoproteins of higher molecular weight, presumably due to the presence of hepatogenous lipoproteins. We studied the removal of 125I-labeled apo B-48 of intestinal lymph chylomicrons from blood plasma of rats. The removal of [14C]cholesteryl esters of biologically labeled chylomicrons was unaffected by radioiodination. The labeled cholesteryl esters and apo B-48 disappeared rapidly from the density (P) less than 1.006 g/ml fraction of plasma. In contrast to the apo B of very low density lipoproteins (1.019 less then p less then 1.063 g/ml) after 1 hr. No 125I was found in the B-100 or B-95 apolipoproteins at any time. We conclude that, unlike the species of apo B found uniquely in hepatogenous very low density lipoproteins, the apo B-48 protein of chylomicrons is not a precursor of the B apoprotein of low density lipoproteins.
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- 1982
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14. LEUPEPTIN AS A TOOL FOR THE DETECTION OF THE SITES OF CATABOLISM OF RAT HIGH-DENSITY LIPOPROTEIN APOLIPOPROTEIN-A-I AND APOLIPOPROTEIN-E
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van't Hooft, F. M., Dallinga-Thie, G. M., van Tol, A., and Other departments
- Published
- 1985
15. Coagulation factor V (Arg(506)-> Gln) mutation and early saphenous vein graft occlusion after coronary artery bypass grafting
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Anders Hamsten, Elisabeth Moor, Angela Silveira, Per Tornvall, Björn Wiman, Margareta Blombäck, van't Hooft F, and Lars Rydén
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Male ,medicine.medical_specialty ,Heterozygote ,medicine.drug_class ,Deep vein ,Glutamine ,Arginine ,Fibrin ,Risk Factors ,Internal medicine ,Occlusion ,medicine ,Factor V Leiden ,Humans ,Point Mutation ,Saphenous Vein ,Coronary Artery Bypass ,Intraoperative Complications ,Aged ,biology ,business.industry ,Anticoagulant ,Factor V ,Graft Occlusion, Vascular ,Hematology ,Middle Aged ,medicine.disease ,Thrombosis ,Hemostasis, Surgical ,Surgery ,surgical procedures, operative ,medicine.anatomical_structure ,Amino Acid Substitution ,biology.protein ,Cardiology ,business ,Protein C ,medicine.drug - Abstract
SummaryThe factor V (Arg506→Gln) mutation confers an increased risk of deep vein thrombosis, whereas its role in saphenous vein graft closure after coronary artery bypass grafting (CABG) remains unclear. This study examined the anticoagulant response to activated protein C (APC ratio) in relation to the surgical trauma and the significance of the factor V Leiden mutation in determining postoperative thrombin generation and fibrin formation and the risk of early vein graft occlusion. A total of 108 men undergoing elective CABG for exertional angina pectoris (mean age 61.1 ± 8.7 years) were examined. The patency of saphenous vein grafts was studied at routine reangiography three months after CABG.Of 100 patients who underwent reangiography, 23 had one or more occluded vein grafts at reangiography. Heterozygosity for the factor V (Arg506→Gln) mutation tended to be associated with early saphenous vein graft occlusion (5/11 carriers vs. 18/89 non-carriers with graft occlusion, व2 = 3.52, p = 0.06), whereas pre- and postoperative APC ratios did not. Pre- and postoperative determinations of prothrombin fragment 1+2, thrombin-antithrombin complexes and soluble fibrin levels did not differ between patients with and without the mutation.Early saphenous vein graft occlusion after CABG could tentatively be added to deep vein thrombosis as a vascular complication that can be attributed to the factor V (Arg506→Gln) mutation.
16. Metabolism of chromatographically separated rat serum lipoproteins specifically labeled with 125I-apolipoprotein E.
- Author
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van't Hooft, F., primary and Havel, R.J., additional
- Published
- 1981
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17. A one-step separation of human serum high density lipoproteins 2 and 3 by rate-zonal density gradient ultracentrifugation in a swinging bucket rotor
- Author
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Groot, P H, primary, Scheek, L M, additional, Havekes, L, additional, van Noort, W L, additional, and van't Hooft, F M, additional
- Published
- 1982
- Full Text
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18. Genome wide association study identifies KCNMA1 contributing to human obesity
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Sørensen Thorkild IA, Hebebrand Johannes, Hansen Torben, Pedersen Oluf, Axelsson Tomas, van't Hooft Ferdinand, Czernichow Sébastien, Dubern Beatrice, Brodin David, Hoffstedt Johan, Arner Peter, Jiao Hong, Kere Juha, Dahlman-Wright Karin, Hamsten Anders, Clement Karine, and Dahlman Ingrid
- Subjects
Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Recent genome-wide association (GWA) analyses have identified common single nucleotide polymorphisms (SNPs) that are associated with obesity. However, the reported genetic variation in obesity explains only a minor fraction of the total genetic variation expected to be present in the population. Thus many genetic variants controlling obesity remain to be identified. The aim of this study was to use GWA followed by multiple stepwise validations to identify additional genes associated with obesity. Methods We performed a GWA analysis in 164 morbidly obese subjects (BMI:body mass index > 40 kg/m2) and 163 Swedish subjects (> 45 years) who had always been lean. The 700 SNPs displaying the strongest association with obesity in the GWA were analyzed in a second cohort comprising 460 morbidly obese subjects and 247 consistently lean Swedish adults. 23 SNPs remained significantly associated with obesity (nominal P< 0.05) and were in a step-wise manner followed up in five additional cohorts from Sweden, France, and Germany together comprising 4214 obese and 5417 lean or population-based control individuals. Three samples, n = 4133, were used to investigate the population-based associations with BMI. Gene expression in abdominal subcutaneous adipose tissue in relation to obesity was investigated for14 adults. Results Potassium channel, calcium activated, large conductance, subfamily M, alpha member (KCNMA1) rs2116830*G and BDNF rs988712*G were associated with obesity in five of six investigated case-control cohorts. In meta-analysis of 4838 obese and 5827 control subjects we obtained genome-wide significant allelic association with obesity for KCNMA1 rs2116830*G with P = 2.82 × 10-10 and an odds ratio (OR) based on cases vs controls of 1.26 [95% C.I. 1.12-1.41] and for BDNF rs988712*G with P = 5.2 × 10-17and an OR of 1.36 [95% C.I. 1.20-1.55]. KCNMA1 rs2116830*G was not associated with BMI in the population-based samples. Adipose tissue (P = 0.0001) and fat cell (P = 0.04) expression of KCNMA1 was increased in obesity. Conclusions We have identified KCNMA1 as a new susceptibility locus for obesity, and confirmed the association of the BDNF locus at the genome-wide significant level.
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- 2011
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19. Genetic studies of body mass index yield new insights for obesity biology
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Locke, Adam E, Kahali, Bratati, Croteau-Chonka, Damien C, Doney, Alex S F, He, Bing, Heikkilä, Outi, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Eklund, Niina, Saraheimo, Markku, Sarti, Cinzia, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Estrada, Karol, Wadén, Johan, Gill, Geoffrey V, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Eury, Elodie, Ladenvall, Claes, Alhenc-Gelas, François, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Folkersen, Lasse, Möllsten, Anna, Cimponeriu, Dan, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Fraser, Ross M, Colhoun, Helen M, Panduru, Nicolae Mircea, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Garcia, Melissa E, Waggott, Daryl, Paterson, Andrew D, Savage, David A, Bain, Stephen C, Martin, Finian, Hirschhorn, Joel N, Godson, Catherine, Florez, Jose C, Groop, Per-Henrik, Maxwell, Alexander P, Geller, Frank, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L, Mora, Samia, Giedraitis, Vilmantas, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Chang, Hsing-Y, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Gigante, Bruna, Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Freitag, Daniel F, Gurdasani, Deepti, Heikkilä, Kauko, Hyppönen, Elina, Isaacs, Aaron, Jackson, Anne U, Esko, Tonu, Go, Alan S, Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Golay, Alain, Mihailov, Evelin, Montasser, May E, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Goodall, Alison H, Service, Susan K, Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Thorleifsson, Gudmar, Gordon, Scott D, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Gorski, Mathias, Been, Latonya F, Bolton, Jennifer L, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doring, Angela, Elliott, Paul, Grabe, Hans-Jörgen, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, 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EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Eriksson, J., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Peacock, M., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., van Meurs JB., Weedon, MN., Wichmann, H., Young, L., Bierut, LJ., Boyd, HA., Econs, MJ., Van T'Hooft, Ferdinand M., Njølstad, Inger, Abecasis, Gonçalo R., Barroso, Inɥ, The MIGEN Consortium, Investigator, Casari, GIORGIO NEVIO, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Landsteiner Laboratory, Clinical Haematology, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life 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Wright, A, Zhang, Q, Brennan, E, Choi, M, Dastani, Z, Drong, A, Eriksson, P, Franco-Cereceda, A, Gadin, J, Gharavi, A, Goddard, M, Handsaker, R, Huang, J, Karpe, F, Kathiresan, S, Keildson, S, Kiryluk, K, Kubo, M, Lee, J, Liang, L, Lifton, R, Ma, B, Mccarroll, S, Mcknight, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Okada, Y, Perry, J, Dorajoo, R, Reinmaa, E, Salem, R, Sandholm, N, Scott, R, Stolk, L, Takahashi, A, Van't Hooft, F, Vinkhuyzen, A, Westra, H, Zheng, W, Zondervan, K, Heath, A, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Bovet, P, Campbell, H, Caulfield, M, Cesana, G, Chakravarti, A, Chasman, D, Chines, P, Collins, F, Crawford, D, Cupples, L, Cusi, D, Danesh, J, de Faire, U, Den Ruijter, H, Dominiczak, A, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Felix, S, Ferrannini, E, Ferrieres, J, Ford, I, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gejman, P, Gieger, C, Gottesman, O, Gudnason, V, Gyllensten, U, Hall, A, Harris, T, Hattersley, A, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Homuth, G, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Illig, T, Jacobs, K, Jarvelin, M, Jockel, K, Johansen, B, Jousilahti, P, Jukema, J, Jula, A, Kaprio, J, Kastelein, J, Keinanen-Kiukaanniemi, S, Kiemeney, L, Knekt, P, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Marchand, L, Lehtimaki, T, Lyssenko, V, Mannisto, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Moll, F, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Madden, P, Pasterkamp, G, Peden, J, Peters, A, Postma, D, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Rioux, J, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schunkert, H, Schwarz, P, Sever, P, Shuldiner, A, Sinisalo, J, Stolk, R, Strauch, K, Tonjes, A, Tregouet, D, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Volker, U, Waeber, G, Willemsen, G, Witteman, J, Zillikens, M, Adair, L, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bornstein, S, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hui, J, Hunter, D, Hveem, K, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, Marz, W, Melbye, M, Metspalu, A, Moebus, S, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Perusse, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sattar, N, Schadt, E, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Walker, M, Wallaschofski, H, Wareham, N, Watkins, H, Weir, D, Wichmann, H, Wilson, J, Zanen, P, Borecki, I, Deloukas, P, Fox, C, Heid, I, O'Connell, J, Strachan, D, Stefansson, K, van Duijn, C, Abecasis, G, Franke, L, Frayling, T, Mccarthy, M, Visscher, P, Scherag, A, Willer, C, Boehnke, M, Mohlke, K, Lindgren, C, Beckmann, J, Barroso, I, North, K, Ingelsson, E, Hirschhorn, J, Loos, R, Speliotes, E, Thompson, J, Goldstein, B, Konig, I, Cazier, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikainen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Claudi-Boehm, S, Cox, D, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schafer, A, Sivananthan, M, Song, C, Stewart, A, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Tsun-Po, Y, Basart, H, Brambilla, P, Cambien, F, Cupples, A, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kahonen, M, Kee, F, Kim, H, 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S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Makinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkila, O, Hietala, K, Kyto, J, Lahermo, P, Lehto, M, Osterholm, A, Parkkonen, M, Pitkaniemi, J, Rosengard-Barlund, M, Saraheimo, M, Sarti, C, Soderlund, J, Soro-Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Waden, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc-Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Mollsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Freitag, D, Gurdasani, D, Heikkila, K, Johnson, T, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Teslovich, T, Van den Herik, E, Volcik, K, Wu, Y, Asiki, G, Been, L, Burnett, M, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Khaw, K, Kim, E, Komulainen, P, Lin, S, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Young, E, Bennett, F, Boomsma, D, Burnier, M, Feranil, A, Freimer, N, Hsiung, C, Kesaniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Meneton, P, Moilanen, L, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton-Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sober, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjogren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland-Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Brown, M, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Staessen, J, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Smith, G, Raffel, L, Yao, J, Schwartz, S, Ikram, M, W, L, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace-Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Wurtz, P, Ong, R, Dorr, M, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Guo, X, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, Palmer, L, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Alizadeh, B, de Boer, R, Boezen, H, Hillege, H, van der Klauw, M, Ormel, J, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Rasmussen-Torvik, L, Lecoeur, C, Johnson, P, Sennblad, B, Salo, P, Timpson, N, Evans, D, St Pourcain, B, Bielak, L, Horikoshi, M, Navarro, P, Raychaudhuri, S, Chen, H, Rybin, D, Willems, S, Song, K, An, P, Marullo, L, Jansen, H, Pankow, J, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Small, K, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Penninx, B, Toenjes, A, Peyser, P, Korner, A, Dupuis, J, Cucca, F, Balkau, B, Bouatia-Naji, N, Purcell, S, Musunuru, K, Ardissino, D, Mannucci, P, Anand, S, Engert, J, Morgan, T, Spertus, J, Stoll, M, Girelli, D, Mckeown, P, Patterson, C, Merlini, P, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Subirana, I, Sala, J, Ramos, R, Williams, G, Nathan, D, Macrae, C, Berglund, G, Asselta, R, Duga, S, Spreafico, M, Daly, M, Nemesh, J, Korn, J, Surti, A, Gianniny, L, Parkin, M, Burtt, N, Gabriel, S, Wright, B, Ball, S, Schunkert, I, Linsel-Nitschke, P, Lieb, W, Fischer, M, Grosshennig, A, Preuss, M, Scholz, M, Chen, Z, Wilensky, R, Matthai, W, Qasim, A, Hakonarson, H, Devaney, J, Pichard, A, Kent, K, Satler, L, Lindsay, J, Waksman, R, Knouff, C, Scheffold, T, Berger, K, Huge, A, Martinelli, N, Olivieri, O, Corrocher, R, Xie, C, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, Di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Yang, T, Higashio, J, Williams, R, Nato, A, Ambite, J, Deelman, E, Manolio, T, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown-Gentry, K, Thornton-Wells, T, Dumitrescu, L, Bush, W, Mitchell, S, Goodloe, R, Wilson, S, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Spencer, K, Pendergrass, S, Le Marchand, L, Park, L, Tiirikainen, M, Kolonel, L, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Anderson, G, Carlson, C, Prentice, R, Lacroix, A, Wu, C, Carty, C, Rosse, S, Young, A, Kocarnik, J, Lin, Y, Jackson, R, Duggan, D, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hankinson, S, Hass, M, Janssens, A, Karasik, D, Keyzer, J, Kiel, D, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Melzer, D, Newman, A, Pare, G, Peeters, P, Pop, V, Raikkonen, K, Salumets, A, Stacey, S, Starr, J, Stathopoulou, M, Styrkarsdottir, U, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Widen, E, Wijnands-Van Gent, C, Yerges-Armstrong, L, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Streeten, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Koller, D, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Couper, D, Easton, D, Foroud, T, Kilpelainen, T, Li, S, Murray, S, Ness, A, Northstone, K, Peacock, M, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segre, A, Sovio, U, Srinivasan, S, Tammesoo, M, van Meurs, J, Young, L, Bierut, L, Econs, M, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International Endogene Consortium, Berndt, Sonja I, Justice, Anne E, Hyppönen, Elina Tuulikki, Epidemiology and Data Science, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
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Male ,LOCI ,Genome-wide association study ,Continental Population Groups/genetics ,VARIANTS ,Body Mass Index ,Insulin Secretion ,Insulin ,Age Factor ,Adiposity ,ddc:616 ,Adipogenesis ,Genetic Predisposition to Disease/genetics ,Synapse ,3. Good health ,Continental Population Group ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,GENOME-WIDE ASSOCIATIONPROVIDES INSIGHTSGLYCEMIC TRAITSLOCIMETAANALYSISVARIANTSINDIVIDUALSHIPPOCAMPALARCHITECTURETOPIRAMATE ,ddc:500 ,Adipogenesis/genetics ,Single Nucleotide/genetics ,Age Factors ,Continental Population Groups ,Energy Metabolism ,Europe ,Female ,Genetic Predisposition to Disease ,Glutamic Acid ,Humans ,Obesity ,Polymorphism, Single Nucleotide ,Quantitative Trait Loci ,Synapses ,Genome-Wide Association Study ,Multidisciplinary ,genetics [Adiposity] ,Human ,Socio-culturale ,genetics [Energy Metabolism] ,ta3111 ,genetic, body mass index, obesity ,SDG 3 - Good Health and Well-being ,GLYCEMIC TRAITS ,genetics [Continental Population Groups] ,Genetic variability ,Polymorphism ,GENOME-WIDE ASSOCIATION ,genetics [Adipogenesis] ,METAANALYSIS ,Genetic association ,Adipogenesi ,genetics [Quantitative Trait Loci] ,ta1184 ,metabolism [Glutamic Acid] ,ta1182 ,PATHWAYS ,metabolism [Synapses] ,ta3121 ,medicine.disease ,metabolism [Insulin] ,Adiposity/genetics ,Clinical Medicine ,Quantitative Trait Loci/genetics ,Body mass index ,HUMAN HEIGHT ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Synapses/metabolism ,Medizin ,Obesity/genetics ,Bioinformatics ,genetic basis ,Obesity/metabolism ,genetics [Obesity] ,body mass index (BMI) ,genetics [Genetic Predisposition to Disease] ,ethnology [Europe] ,2. Zero hunger ,Genetics ,ARCHITECTURE ,Genetics of obesity ,Medicine (all) ,Single Nucleotide ,Polymorphism, Single Nucleotide/genetics ,Insulin/metabolism/secretion ,Glutamic Acid/metabolism ,genetics [Polymorphism, Single Nucleotide] ,EXPRESSION ,Insulin/metabolism ,PROVIDES INSIGHTS ,genetics [Racial Groups] ,Biology ,Obesity/genetics/metabolism ,Europe/ethnology ,metabolism [Obesity] ,Mendelian randomization ,medicine ,Energy Metabolism/genetics ,body mass, genetic analysis, obesity ,Klinisk medicin - Abstract
Item does not contain fulltext Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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- 2015
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20. Angiopoietin-like protein 8 differentially regulates ANGPTL3 and ANGPTL4 during postprandial partitioning of fatty acids.
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Chen YQ, Pottanat TG, Siegel RW, Ehsani M, Qian YW, Zhen EY, Regmi A, Roell WC, Guo H, Luo MJ, Gimeno RE, Van't Hooft F, and Konrad RJ
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- Angiopoietin-Like Protein 3, Angiopoietin-Like Protein 8, Biomarkers metabolism, Humans, Angiopoietin-Like Protein 4 metabolism, Angiopoietin-like Proteins metabolism, Fatty Acids metabolism, Peptide Hormones metabolism, Postprandial Period
- Abstract
Angiopoietin-like protein (ANGPTL)8 has been implicated in metabolic syndrome and reported to regulate adipose FA uptake through unknown mechanisms. Here, we studied how complex formation of ANGPTL8 with ANGPTL3 or ANGPTL4 varies with feeding to regulate LPL. In human serum, ANGPTL3/8 and ANGPTL4/8 complexes both increased postprandially, correlated negatively with HDL, and correlated positively with all other metabolic syndrome markers. ANGPTL3/8 also correlated positively with LDL-C and blocked LPL-facilitated hepatocyte VLDL-C uptake. LPL-inhibitory activity of ANGPTL3/8 was >100-fold more potent than that of ANGPTL3, and LPL-inhibitory activity of ANGPTL4/8 was >100-fold less potent than that of ANGPTL4. Quantitative analyses of inhibitory activities and competition experiments among the complexes suggested a model in which localized ANGPTL4/8 blocks the LPL-inhibitory activity of both circulating ANGPTL3/8 and localized ANGPTL4, allowing lipid sequestration into fat rather than muscle during the fed state. Supporting this model, insulin increased ANGPTL3/8 secretion from hepatocytes and ANGPTL4/8 secretion from adipocytes. These results suggest that low ANGPTL8 levels during fasting enable ANGPTL4-mediated LPL inhibition in fat tissue to minimize adipose FA uptake. During feeding, increased ANGPTL8 increases ANGPTL3 inhibition of LPL in muscle via circulating ANGPTL3/8, while decreasing ANGPTL4 inhibition of LPL in adipose tissue through localized ANGPTL4/8, thereby increasing FA uptake into adipose tissue. Excessive caloric intake may shift this system toward the latter conditions, possibly predisposing to metabolic syndrome., (Copyright © 2020 Chen et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.)
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- 2020
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21. PLA2G10 Gene Variants, sPLA2 Activity, and Coronary Heart Disease Risk.
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Guardiola M, Exeter HJ, Perret C, Folkersen L, Van't Hooft F, Eriksson P, Franco-Cereceda A, Paulsson-Berne G, Palmen J, Li K, Cooper JA, Khaw KT, Mallat Z, Ninio E, Karabina SA, Humphries SE, Boekholdt SM, Holmes MV, and Talmud PJ
- Subjects
- Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Male, Meta-Analysis as Topic, Middle Aged, Prospective Studies, Risk Factors, Coronary Disease blood, Coronary Disease enzymology, Coronary Disease genetics, Group X Phospholipases A2 blood, Group X Phospholipases A2 genetics, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable
- Abstract
Background: Observational studies report that secretory phospholipase A2 (sPLA2) activity is a marker for coronary heart disease (CHD) risk, and activity measures are thought to represent the composite activity of sPLA2-IIA, -V, and -X. The aim of this study was to use genetic variants of PLA2G10, encoding sPLA2-X, to investigate the contribution of sPLA2-X to the measure of sPLA2 activity and coronary heart disease (CHD) risk traits and outcome., Methods and Results: Three PLA2G10 tagging single-nucleotide polymorphisms (rs72546339, rs72546340, and rs4003232) and a previously studied PLA2G10 coding single-nucleotide polymorphism rs4003228, R38C, were genotyped in a nested case: control cohort drawn from the prospective EPIC-Norfolk Study (2175 cases and 2175 controls). Meta-analysis of rs4003228 (R38C) and CHD was performed using data from the Northwick Park Heart Study II and 2 published cohorts AtheroGene and SIPLAC, providing in total an additional 1884 cases and 3119 controls. EPIC-Norfolk subjects in the highest tertile of sPLA2 activity were older and had higher inflammatory markers compared with those in the lowest tertile for sPLA2 activity. None of the PLA2G10 tagging single-nucleotide polymorphism nor R38C, a functional variant, were significantly associated with sPLA2 activity, intermediate CHD risk traits, or CHD risk. In meta-analysis, the summary odds ratio for R38C was odds ratio=0.97 (95% confidence interval, 0.77-1.22)., Conclusions: PLA2G10 variants are not significantly associated with plasma sPLA2 activity or with CHD risk., (© 2015 American Heart Association, Inc.)
- Published
- 2015
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22. TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content.
- Author
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Mahdessian H, Taxiarchis A, Popov S, Silveira A, Franco-Cereceda A, Hamsten A, Eriksson P, and van't Hooft F
- Subjects
- Animals, Cattle, Cell Line, Tumor, Dogs, Endoplasmic Reticulum metabolism, Gene Expression Profiling, Genome-Wide Association Study, Genotype, Golgi Apparatus metabolism, Guinea Pigs, Hep G2 Cells, Humans, Lipids chemistry, Mice, Quantitative Trait Loci, RNA, Small Interfering metabolism, Rats, Tissue Distribution, Triglycerides metabolism, Gene Expression Regulation, Lipid Metabolism, Liver metabolism, Membrane Proteins genetics, Membrane Proteins physiology
- Abstract
Genome-wide association studies have identified a locus on chromosome 19 associated with plasma triglyceride (TG) concentration and nonalcoholic fatty liver disease. However, the identity and functional role of the gene(s) responsible for these associations remain unknown. Of 19 expressed genes contained in this locus, none has previously been implicated in lipid metabolism. We performed gene expression studies and expression quantitative trait locus analysis in 206 human liver samples to identify the putative causal gene. Transmembrane 6 superfamily member 2 (TM6SF2), a gene with hitherto unknown function, expressed predominantly in liver and intestine, was identified as the putative causal gene. TM6SF2 encodes a protein of 351 amino acids with 7-10 predicted transmembrane domains. Otherwise, no other protein features were identified which could help to elucidate the function of TM6SF2. Protein subcellular localization studies with confocal microscopy demonstrated that TM6SF2 is localized in the endoplasmic reticulum and the ER-Golgi intermediate compartment of human liver cells. Functional studies for secretion of TG-rich lipoproteins (TRLs) and lipid droplet content were performed in human hepatoma Huh7 and HepG2 cells using confocal microscopy and siRNA inhibition and overexpression techniques. In agreement with the genome-wide association data, it was found that TM6SF2 siRNA inhibition was associated with reduced secretion of TRLs and increased cellular TG concentration and lipid droplet content, whereas TM6SF2 overexpression reduced liver cell steatosis. We conclude that TM6SF2 is a regulator of liver fat metabolism with opposing effects on the secretion of TRLs and hepatic lipid droplet content.
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- 2014
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23. Novel genetic approach to investigate the role of plasma secretory phospholipase A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian randomization analysis using PLA2G5 expression levels.
- Author
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Holmes MV, Exeter HJ, Folkersen L, Nelson CP, Guardiola M, Cooper JA, Sofat R, Boekholdt SM, Khaw KT, Li KW, Smith AJ, Van't Hooft F, Eriksson P, Franco-Cereceda A, Asselbergs FW, Boer JM, Onland-Moret NC, Hofker M, Erdmann J, Kivimaki M, Kumari M, Reiner AP, Keating BJ, Humphries SE, Hingorani AD, Mallat Z, Samani NJ, and Talmud PJ
- Subjects
- Alleles, Case-Control Studies, Coronary Disease blood, Genotype, Group V Phospholipases A2 blood, Humans, Isoenzymes blood, Isoenzymes genetics, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Coronary Disease enzymology, Coronary Disease genetics, Group V Phospholipases A2 genetics
- Abstract
Background: Secretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis., Methods and Results: Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotide polymorphism in PLA2G5 showing the strongest association with PLA2G5 mRNA expression levels as a proxy for sPLA2-V levels. We tested the association of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 case-control studies with 27 230 events and 70 500 controls. rs525380C>A showed the strongest association with PLA2G5 mRNA expression (P=5.1×10(-6)). There was no association of rs525380C>A with plasma sPLA2 activity (difference in geometric mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidence intervals [-0.9%, 1.6%]; P=0.56). In meta-analyses, the odds ratio for CHD per A-allele was 1.02 (95% confidence intervals [0.99, 1.04]; P=0.20)., Conclusions: This novel approach for single-nucleotide polymorphism selection for this modified Mendelian randomization analysis showed no association between rs525380 (the lead single-nucleotide polymorphism for PLA2G5 expression, a surrogate for sPLA2-V levels) and CHD events. The evidence does not support a causal role for sPLA2-V in CHD.
- Published
- 2014
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24. Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease.
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Folkersen L, van't Hooft F, Chernogubova E, Agardh HE, Hansson GK, Hedin U, Liska J, Syvänen AC, Paulsson-Berne G, Franco-Cereceda A, Hamsten A, Gabrielsen A, and Eriksson P
- Subjects
- Aged, Female, Genes, Genome-Wide Association Study methods, Genotype, Humans, Linkage Disequilibrium, Male, Middle Aged, Oligonucleotide Array Sequence Analysis methods, Risk, Cardiovascular Diseases genetics, Genetic Predisposition to Disease genetics, Polymorphism, Single Nucleotide physiology
- Abstract
Background: Population-based genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with cardiovascular disease or its risk factors. Genes in close proximity to these risk-SNPs are often thought to be pathogenetically important based on their location alone. However, the actual connections between SNPs and disease mechanisms remain largely unknown., Methods and Results: To identify novel susceptibility genes, we investigated how 166 SNPs previously found to be associated with increased cardiovascular risk and/or predisposing metabolic traits relate to the expression of nearby genes. Gene expression in 577 samples of aorta, liver, mammary artery, and carotid atherosclerotic plaque was measured using expression arrays. For 47 SNPs, the expression levels of proximal genes (located within 200 kb) were affected (P<0.005). More than 20 of these genes had not previously been identified as candidate genes for cardiovascular or related metabolic traits. SNP-associated gene effects were tissue-specific and the tissue specificity was phenotype-dependent., Conclusions: This study demonstrates several instances of association between risk-SNPs and genes immediately adjacent to them. It also demonstrates instances in which the associated gene is not the immediately proximal and obvious candidate gene for disease. This shows the necessity of careful studies of genetic marker data as a first step toward application of genome-wide association studies findings in a clinical setting.
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- 2010
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25. Mutation in the sterol 27-hydroxylase gene associated with fatal cholestasis in infancy.
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von Bahr S, Björkhem I, Van't Hooft F, Alvelius G, Nemeth A, Sjövall J, and Fischler B
- Subjects
- Cholestanetriol 26-Monooxygenase, DNA Mutational Analysis, Exons, Fatal Outcome, Humans, Infant, Infant, Newborn, Male, Mutation, Polymerase Chain Reaction, Xanthomatosis, Cerebrotendinous genetics, Cholestasis genetics, Steroid Hydroxylases genetics, Xanthomatosis, Cerebrotendinous diagnosis
- Abstract
Background: Inborn errors of bile acid synthesis are rare but potentially treatable causes of neonatal cholestasis. We here present a cholestatic infant with an ongoing cytomegalovirus infection who despite intensive treatment died of severe liver disease at 4 months of age., Methods: The urinary steroids were investigated by electrospray mass spectrometry and gas chromatography mass spectrometry. Oxysterols in plasma were analysed by isotope dilution mass spectrometry. Mutations in the sterol 27-hydroxylase gene were detected by PCR., Results: Glucuronidated bile alcohols, which are known to be excreted by patients with cerebrotendinous xanthomatosis (CTX) were detected in the urine. Analysis of plasma revealed markedly reduced levels of 27-hydroxycholesterol. Mutation analysis showed the presence of a stop codon in exon 7, confirming the diagnosis of CTX, a rare disease not previously diagnosed in Sweden., Conclusions: Fetal and neonatal deaths among siblings of patients with CTX have been reported previously and the present case supports the contention that reduced activity of the sterol 27-hydroxylase may predispose to the development of neonatal cholestasis. The associated viral infection may have further precipitated the liver disease. Since CTX, like other inborn errors of bile acid synthesis may be treated with bile acids an early diagnosis is essential. Thus, the analysis of urine by electrospray mass spectrometry is highly recommended in the investigation of patients with neonatal cholestasis.
- Published
- 2005
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26. Functional characterization of 4 polymorphisms in promoter region of hepatic lipase gene.
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van't Hooft FM, Lundahl B, Ragogna F, Karpe F, Olivecrona G, and Hamsten A
- Subjects
- Adult, Alleles, Binding Sites, DNA metabolism, Genotype, Humans, Linkage Disequilibrium, Male, Middle Aged, Mutagenesis, Site-Directed, Nuclear Proteins metabolism, Sequence Analysis, DNA, Transcription, Genetic, Transfection, Lipase genetics, Liver enzymology, Polymorphism, Restriction Fragment Length, Promoter Regions, Genetic
- Abstract
Hepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of plasma lipoproteins, especially high density lipoproteins. Association studies have provided strong evidence for relations of common mutations in the promoter region of the HL gene to postheparin plasma HL activity and the plasma high density lipoprotein cholesterol concentration, but the functional relevance of these polymorphisms has not been evaluated to date. We analyzed the physiological significance of 4 common polymorphisms (-250G/A, -514C/T, -710T/C, and -763A/G, all in strong linkage disequilibrium) in the promoter of the HL gene by use of electrophoretic mobility shift assays and transient transfection studies in HepG2 cells. No consistent evidence was found for a significant contribution of any of these polymorphisms to the basal rate of transcription of the HL gene. These data suggest that the 4 polymorphisms in the promoter region of the HL gene are in linkage disequilibrium with >/=1 as-yet-unknown functional polymorphisms in the HL gene locus with a significant effect on HL metabolism and/or enzymatic activity.
- Published
- 2000
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27. A common functional polymorphism (C-->A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha.
- Author
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Skoog T, van't Hooft FM, Kallin B, Jovinge S, Boquist S, Nilsson J, Eriksson P, and Hamsten A
- Subjects
- Adult, Alleles, Binding Sites genetics, Gene Expression Regulation, Gene Frequency, Genotype, Humans, Linkage Disequilibrium, Male, Middle Aged, Monokines genetics, Nuclear Proteins metabolism, Point Mutation, Polymorphism, Genetic, Protein Binding, Transcription, Genetic genetics, Tumor Cells, Cultured, Monokines blood, Promoter Regions, Genetic genetics, Tumor Necrosis Factor-alpha genetics
- Abstract
Tumour necrosis factor-alpha (TNF-alpha) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF-alpha has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance. The regulation of TNF-alpha expression in man is indicated to be partly genetically determined. We therefore screened a 1263 bp section of the proximal promoter of the TNF-alpha gene for common genetic variants affecting the transcriptional activity of the gene. Here we report the characterization of a common functional polymorphism in the promoter region of the TNF-alpha gene, a C-->A substitution at position -863. Electromobility shift assays provided evidence for a distinct difference in the binding of monocytic and hepatic nuclear factors to the -863C and -863A alleles. The rare -863A allele was associated with 31% lower transcriptional activity ( P < 0.001) in chloramphenicol acetyltransferase (CAT) reporter gene studies in human hepatoblastoma (HepG2) cells, indicating that the-863C/A polymorphism influences the basal rate of transcription of the TNF-alpha gene in vitro. Allele frequencies were 0.83/0.17 amongst 254 apparently healthy men of Swedish origin, aged 35-50 years. In 156 men, the -863C/A polymorphism was associated with the serum TNF-alpha concentration, carriers of the rare A allele having a significantly lower TNF-alpha level ( P < 0.05). It is concluded that the common-863C/A polymorphism in the promoter region of the TNF-alpha gene is functional in vitro in monocytic and hepatic cells and influences the serum TNF-alpha concentration in vivo in healthy middle-aged men.
- Published
- 1999
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28. Coagulation factor V (Arg506-->Gln) mutation and early saphenous vein graft occlusion after coronary artery bypass grafting.
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Moor E, Silveira A, van't Hooft F, Tornvall P, Blombäck M, Wiman B, Rydén L, and Hamsten A
- Subjects
- Aged, Arginine, Glutamine, Hemostasis, Surgical, Heterozygote, Humans, Intraoperative Complications, Male, Middle Aged, Risk Factors, Amino Acid Substitution, Coronary Artery Bypass, Factor V genetics, Graft Occlusion, Vascular genetics, Point Mutation, Saphenous Vein transplantation
- Abstract
The factor V (Arg506-->Gln) mutation confers an increased risk of deep vein thrombosis, whereas its role in saphenous vein graft closure after coronary artery bypass grafting (CABG) remains unclear. This study examined the anticoagulant response to activated protein C (APC ratio) in relation to the surgical trauma and the significance of the factor V Leiden mutation in determining postoperative thrombin generation and fibrin formation and the risk of early vein graft occlusion. A total of 108 men undergoing elective CABG for exertional angina pectoris (mean age 61.1 +/- 8.7 years) were examined. The patency of saphenous vein grafts was studied at routine reangiography three months after CABG. Of 100 patients who underwent reangiography, 23 had one or more occluded vein grafts at reangiography. Heterozygosity for the factor V (Arg506-->Gln) mutation tended to be associated with early saphenous vein graft occlusion (5/11 carriers vs. 18/89 non-carriers with graft occlusion, chi2 = 3.52, p = 0.06), whereas pre- and postoperative APC ratios did not. Pre- and postoperative determinations of prothrombin fragment 1+2, thrombin-antithrombin complexes and soluble fibrin levels did not differ between patients with and without the mutation. Early saphenous vein graft occlusion after CABG could tentatively be added to deep vein thrombosis as a vascular complication that can be attributed to the factor V (Arg506-->Gln) mutation.
- Published
- 1998
29. Separation of VLDL subfractions by density gradient ultracentrifugation.
- Author
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Zhao SP, Bastiaanse EM, Hau MF, Smelt AH, Gevers Leuven JA, Van der Laarse A, and Van't Hooft FM
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Centrifugation, Density Gradient methods, Hyperlipoproteinemias blood, Lipoproteins, VLDL analysis, Lipoproteins, VLDL classification, Ultracentrifugation methods
- Abstract
To assess the presence and composition of very-low-density lipoprotein (VLDL) in various types of hyperlipoproteinemia, a method of density gradient ultracentrifugation has been developed. After 2 hours of density gradient ultracentrifugation, human serum VLDL is separated into two distinct VLDL cholesterol peaks (VLDL1 and VLDL2). The two VLDL subfractions were detected in the serum samples from all subjects in the study, including subjects with normolipidemia (n = 10), familial dysbetalipoproteinemia (n = 12), and type IIa (n = 8), type IIb (n = 12), and type IV/V (n = 10) hyperlipoproteinemia. The cholesterol profiles obtained by the density gradient ultracentrifugation technique resembled the band patterns after electrophoresis of identical serum samples on 2% to 16% nondenaturing polyacrylamide gradient gel: VLDL1 represents relatively large VLDL particles (diameter of about 67 nm) and VLDL2 represents relatively small VLDL particles (diameter of about 38 nm). Recentrifugation of isolated VLDL1 and isolated VLDL2 did not result in any change in their density distribution. In all groups studied, the fluidity of VLDL1 was significantly higher than that of VLDL2, in accordance with the finding that VLDL1 particles were relatively rich in triglycerides and VLDL2 particles were relatively rich in cholesteryl esters. These results indicate that the two VLDL subfractions isolated represent distinct VLDL subclasses. The density gradient ultracentrifugation technique presented in this study allows the rapid isolation and characterization of VLDL subfractions from the serum samples of normolipidemic individuals and patients with hyperlipoproteinemia.
- Published
- 1995
30. Coagulation factor VII mass and activity in young men with myocardial infarction at a young age. Role of plasma lipoproteins and factor VII genotype.
- Author
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Moor E, Silveira A, van't Hooft F, Suontaka AM, Eriksson P, Blombäck M, and Hamsten A
- Subjects
- Adult, Factor VII genetics, Genotype, Humans, Lipoproteins, IDL, Lipoproteins, LDL blood, Lipoproteins, VLDL blood, Male, Multivariate Analysis, Polymorphism, Genetic, Reference Values, Factor VII analysis, Factor VII physiology, Lipoproteins blood, Myocardial Infarction blood, Myocardial Infarction physiopathology
- Abstract
Factor VII (FVII) coagulant activity has been proven to be associated with the risk of future fatal coronary heart disease (CHD) in middle-aged men. Recent studies have emphasized the role of triglyceride-rich lipoproteins and FVII genotype in determining plasma levels of FVII protein and activity. The present study was undertaken to examine whether FVII activity state and protein concentration in fasting plasma are altered in young men with proven myocardial infarction (MI) and examined the relations of FVII to subfractions of apo B-containing lipoproteins and the Arg-->Gln polymorphism in the FVII gene. Activated FVII (FVIIa) was determined by a clotting assay using soluble, recombinant, truncated tissue factor. A total of 94 men with a first MI before the age of 45 (mean age +/- SD, 39.6 +/- 4.5 years) were included in the study along with 99 population-based, age-matched control subjects. In addition to FVIIa and FVII antigen (FVII:Ag), a panel of FVII activity assays were included for comparison with previous work in this field. The plasma level of FVII:Ag was higher in patients than in control subjects when the entire groups were compared (537 +/- 128 versus 479 +/- 93 ng/mL, P < .001), the differences being accounted for by patients with hypertriglyceridemic lipoprotein phenotypes. In contrast, FVIIa was similar in patients and control subjects (4.6 +/- 1.4 versus 4.3 +/- 1.3 ng/mL, NS), which means that the proportion of FVIIa molecules was unaltered or even lower in the patients. As expected, the Arg-->Gln polymorphism significantly influenced both FVII mass and activity levels. In addition, presence of the Gln allele appeared to be associated with a lower proportion of fully active FVII molecules. The polymorphism also affected the relation between the plasma concentration of VLDL and FVII:Ag. The triglyceride content and particle number of all VLDL subfractions, irrespective of particle size, correlated fairly strongly with FVII mass determinations but not at all with FVIIa. HDL cholesterol concentration, on the other hand, presumably reflecting the efficiency of lipoprotein lipase-mediated lipolysis of VLDL, related significantly to the FVIIa level. The Arg-->Gln polymorphism, independent of lipoprotein effects, explained 5% to 10% of the variation in FVII mass and activity. In conclusion, the present findings speak against a role of FVII as a risk factor for CHD, because a significantly increased potential for activation of coagulation (ie, raised basal concentration of FVIIa) was not observed among young postinfarction patients.(ABSTRACT TRUNCATED AT 400 WORDS)
- Published
- 1995
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31. Characterization of five new mutants in the carboxyl-terminal domain of human apolipoprotein E: no cosegregation with severe hyperlipidemia.
- Author
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van den Maagdenberg AM, Weng W, de Bruijn IH, de Knijff P, Funke H, Smelt AH, Gevers Leuven JA, van't Hooft FM, Assmann G, and Hofker MH
- Subjects
- Adult, Aged, Aged, 80 and over, Alleles, Amino Acid Sequence, Apolipoproteins E chemistry, Base Sequence, Child, DNA Mutational Analysis, Electrophoresis, Polyacrylamide Gel methods, Female, Humans, Isoelectric Focusing, Male, Middle Aged, Molecular Sequence Data, Nucleic Acid Denaturation, Pedigree, Polymerase Chain Reaction, Recombination, Genetic, Apolipoproteins E genetics, Genetic Variation, Hyperlipoproteinemias genetics, Mutation
- Abstract
Assessment of the apolipoprotein E (apoE) phenotype by isoelectric focusing of both hyperlipidemic and normolipidemic individuals identified five new variants. All mutations were confined to the downstream part of the APOE gene by using denaturing gradient gel electrophoresis (DGGE). Sequence analysis revealed five new mutations causing unique amino acid substitutions in the carboxyl-terminal part of the protein containing the putative lipid-binding domain. Three hyperlipoproteinemic probands were carriers of the APOE*2(Val236-->Glu) allele, the APOE*3(Cys112-->Arg; Arg251-->Gly) allele, or the APOE*1(Arg158-->Cys; Leu252-->Glu) allele. DGGE of the region encoding the receptor-binding domain was useful for haplotyping the mutations at codons 112 and 158. Family studies failed to demonstrate cosegregation between the new mutations and severe hyperlipoproteinemia, although a number of carriers for the APOE*3(Cys112-->Arg; Arg251-->Gly) allele and the APOE*1(Arg158-->Cys; Leu252-->Glu) allele expressed hypertriglyceridemia and/or hypercholesterolemia. Two other mutant alleles, APOE*4-(Cys112-->Arg; Arg274-->His) and APOE*4+(Ser296-->Arg), were found in normolipidemic probands. The lack of cosegregation of these new mutations with severe hyperlipoproteinemia suggests that these mutations do not exert a dominant effect on the functioning of apoE.
- Published
- 1993
32. Potential of 99mTc-LDLs labeled by two different methods for scintigraphic detection of experimental atherosclerosis in rabbits.
- Author
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Atsma DE, Feitsma RI, Camps J, van't Hooft FM, van der Wall EE, Nieuwenhuizen W, and Pauwels EK
- Subjects
- Animals, Aorta diagnostic imaging, Dithionite, Male, Rabbits, Radionuclide Imaging, Arteriosclerosis diagnostic imaging, Borohydrides, Lipoproteins, LDL, Organotechnetium Compounds, Tin, Tin Compounds
- Abstract
In this study we evaluated two different 99mTc-labeling techniques to produce 99mTc-low density lipoprotein (99mTc-LDL) suitable for the scintigraphic delineation of experimental atherosclerotic lesions. The two methods are 1) a procedure that uses stannous chloride and sodium borohydride (borohydride method) and 2) a procedure that uses sodium dithionite as a reducing agent and that has been successfully applied in previous scintigraphic atherosclerosis detection (dithionite method). 99mTc-LDL produced by either method was injected into New Zealand White rabbits with diet-induced atherosclerotic plaques and in control rabbits. Scintigraphic images were taken 10 minutes (t = 0) and 1, 4, 8, 16, and 24 hours after injection. Clearance of plasma radioactivity was also studied. Stability of the 99mTc-LDL complex in the circulation was examined by size exclusion chromatography of plasma samples. After scintigraphy, the animals were killed, and the biodistribution of radioactivity was determined. The thoracic and abdominal aortas appeared in scintigraphic images to accumulate 99mTc over their entire length with either 99mTc-LDL preparation. The sparse imaging of focal atherosclerosis was found to be due to the fact that the aortas were covered with confluent atherosclerotic lesions. Scintigraphic image analysis showed that 24 hours after injection, the accumulated radioactivity in the abdominal aorta of the atherosclerotic rabbits was 57% and 54%, respectively, of the accumulated radioactivity in the abdominal aorta at t = 0 when the borohydride versus the dithionite method was used. In the control animals this value was 25% for the dithionite method, whereas in the borohydride method the aortas could not be detected in the images at t = 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
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33. Comparison of the metabolic behavior of rat apolipoproteins A-I and A-IV, isolated from both lymph chylomicrons and serum high density lipoproteins.
- Author
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Dallinga-Thie GM, van't Hooft FM, and van Tol A
- Subjects
- Animals, Apolipoprotein A-I, Apolipoproteins A isolation & purification, Isoelectric Focusing, Kidney metabolism, Kinetics, Lipoproteins, HDL blood, Liver metabolism, Male, Molecular Weight, Rats, Rats, Inbred Strains, Apolipoproteins A metabolism, Chylomicrons metabolism, Lipoproteins, HDL metabolism, Lymph metabolism
- Abstract
Rat apolipoprotein (apo) A-I and A-IV, isolated from both lymph chylomicrons and serum high density lipoproteins (HDL) were analyzed by isoelectric focusing. Lymph chylomicron apo A-I consisted for 81 +/- 2% of the pro form and for 19 +/- 2% of the mature form, while apo A-I isolated from serum HDL was present for 36 +/- 4% in the pro form and for 64 +/- 4% in the mature form. Apo A-IV also showed two major protein bands after analysis by isoelectric focusing. The most prominent component is the more basic protein that amounts to 80 +/- 2% in apo A-IV isolated from lymph chylomicrons and to 60 +/- 3% in apo A-IV isolated from serum HDL. Apo A-I (or apo A-IV), isolated from both sources (lymph chylomicrons or serum HDL), was iodinated and the radioactive apolipoproteins were incorporated into rat serum lipoproteins. The resulting labeled HDL was isolated from serum by molecular sieve chromatography on 6% agarose columns and injected intravenously into rats. No difference in the fractional turnover rate or the tissue uptake of the two labeled HDL preparations was observed, neither for apo A-I nor for apo A-IV. It is concluded that the physiological significance of the extracellular pro apo A-I conversion or the post-translational modification of apo A-IV is not related to the fractional turnover rate in serum or to the rate of catabolism in liver and kidneys.
- Published
- 1986
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34. Distribution of apolipoproteins A-I and A-IV among lipoprotein classes in rat mesenteric lymph, fractionated by molecular sieve chromatography.
- Author
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Dallinga-Thie GM, van Tol A, van't Hooft FM, and Groot PH
- Subjects
- Absorption, Animals, Apolipoprotein A-I, Apolipoproteins metabolism, Biological Transport, Chromatography, Gel, Chylomicrons analysis, Glucose metabolism, Lipid Metabolism, Male, Mesentery analysis, Rats, Rats, Inbred Strains, Triglycerides metabolism, Apolipoproteins A analysis, Lymph analysis
- Abstract
The distribution of apolipoproteins A-I and A-IV among lymph lipoprotein fractions was studied after separation by molecular sieve chromatography, avoiding any ultracentrifugation. Lymph was obtained from rats infused either with a glucose solution or with a triacylglycerol emulsion. Relative to glucose infusion, triacylglycerol infusion caused a 20-fold increase in the output of triacylglycerol, coupled with a 4-fold increase in output of apolipoprotein A-IV. The output of apolipoprotein A-I was only elevated 2-fold. Chromatography on 6% agarose showed that lymph apolipoproteins A-I and A-IV are present on triacylglycerol-rich particles and on particles of the size of HDL. In addition, apolipoprotein A-IV is also present as 'free' apolipoprotein A-IV. The increase in apolipoprotein A-I output is caused by a higher output of A-I associated with large chylomicrons only, while the increase in apolipoprotein A-IV output is reflected by an increased output in all lymph lipoprotein fractions, including lymph HDL and 'free' apolipoprotein A-IV. The increased level of 'free' A-IV, seen in fatty lymph, may contribute to, and at least partly explain, the high concentrations of 'free' apolipoprotein A-IV present in serum obtained from fed animals.
- Published
- 1986
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35. The sites of degradation of purified rat low density lipoprotein and high density lipoprotein in the rat.
- Author
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van't Hooft FM and van Tol A
- Subjects
- Animals, Chromatography, Affinity, Female, Humans, Iodine Radioisotopes, Kinetics, Lipoproteins, HDL isolation & purification, Lipoproteins, LDL isolation & purification, Male, Pregnancy, Rats, Rats, Inbred Strains, Lipoproteins, HDL blood, Lipoproteins, LDL blood
- Abstract
Low density lipoprotein and high density lipoprotein were isolated from rat serum by sequential ultracentrifugation in the density intervals 1.025-1.050 g/ml and 1.125-1.21 g/ml, respectively. The isolated lipoproteins were radioiodinated using ICl. Low density lipoprotein was further purified by concanavalin A affinity chromatography and concentrated by ultracentrifugation. 95% of the purified low density lipoprotein radioactivity was precipitable by tetramethylurea, while only 4% was associated with lipids. The radioiodinated high density lipoprotein was incubated for 1 h at 4 degrees C with unlabelled very low density lipoprotein, followed by reisolation by sequential ultracentrifugation. Only 3% of the radioactivity was associated with lipids and 90% was present on apolipoprotein A-I. The serum decay curves of labelled and subsequently purified rat low and high density lipoprotein, measured over a period of 28 h, clearly exhibited more than one component, in contrast to the monoexponential decay curves of iodinated human low density lipoprotein. The decay curves were not affected by the methods used to purify the LDL and HDL preparations. The catabolic sites of the labelled rat lipoproteins were analyzed in vivo using leupeptin-treated rats. In vivo treatment of rats with leupeptin did not affect the rate of disappearance from serum of intravenously injected labelled rat low density lipoprotein and high density lipoprotein. Leupeptin-dependent accumulation of radioiodine occurred almost exclusively in the liver after intravenous injection of iodinated low density lipoprotein, while both the liver and the kidneys showed leupeptin-dependent accumulation of radioactivity after injection of iodinated high density lipoprotein.
- Published
- 1985
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36. Discrepancies in the catabolic pathways of human and rat high-density lipoprotein apolipoprotein A-I in the rat.
- Author
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van't Hooft FM and van Tol A
- Subjects
- Animals, Apolipoprotein A-I, Humans, Kidney metabolism, Kinetics, Leupeptins pharmacology, Liver metabolism, Male, Rats, Rats, Inbred Strains, Species Specificity, Tissue Distribution, Apolipoproteins A metabolism, Lipoproteins, HDL metabolism
- Abstract
The in vivo metabolism in the rat of radioiodinated human and rat high-density lipoprotein was compared with a double-label procedure using 125I and 131I. While rat high-density lipoprotein showed a biphasic serum decay, human high-density lipoprotein was characterized by a monoexponential serum decay. No differences were observed between the serum decay of human high-density lipoprotein-2 and -3 subfractions, isolated by rate zonal ultracentrifugation. The catabolic sites of human and rat high-density lipoprotein were analysed using the lysosomal cathepsin inhibitor leupeptin. Radioiodinated rat high-density lipoprotein was catabolized by the kidneys and by the liver. In contrast, radioiodinated human high-density lipoprotein was catabolized almost exclusively in the liver. No difference in the catabolic sites of human high-density lipoprotein-2 and -3 subfractions was observed. The catabolic sites of human high-density lipoprotein apolipoprotein A-I in the rat were further analysed using the O-(4-diazo-3-[125I]iodobenzoyl) sucrose label. Compared with rat high-density lipoprotein apolipoprotein A-I, the kidneys played a minor role in the catabolism of human high-density lipoprotein apolipoprotein A-I. It is concluded that in the rat the catabolic pathways of the apolipoprotein A-I moieties of rat and human high-density lipoproteins are different, indicating that homologous high-density lipoproteins should be used for the investigation of in vivo metabolism.
- Published
- 1985
- Full Text
- View/download PDF
37. Effect of 17 alpha-ethinylestradiol on the catabolism of high-density lipoprotein apolipoprotein A-I in the rat.
- Author
-
van't Hooft FM, van Gent T, and van Tol A
- Subjects
- Animals, Apolipoprotein A-I, Liver drug effects, Liver metabolism, Organ Size drug effects, Protein Binding drug effects, Rats, Rats, Inbred Strains, Apolipoproteins A metabolism, Ethinyl Estradiol pharmacology, Lipoproteins, HDL metabolism
- Abstract
The in vivo metabolism and tissue sites of catabolism of high-density lipoproteins (HDL), labelled specifically in the apolipoprotein (apo) A-I moiety, were studied in rats treated with 17 alpha-ethinylestradiol (EE) for 5 days. Apo A-I was labelled either with O-(4-diazo-3-[125I]iodobenzoyl)sucrose, a non-degradable labelling compound, or with 131ICl. It was found that EE treatment decreases the serum cholesterol concentration to 10 mg/dl and stimulates the serum decay of apo A-I labelled HDL. The latter effect could be attributed to an increased catabolism of apo A-I labelled HDL in the liver. The increased rates of the serum decay and tissue uptake of apo A-I labelled HDL in EE-treated rats were not affected by a bolus injection of unlabelled human low-density lipoprotein (LDL), administered at the time of the injection of the labelled HDL. When the serum cholesterol concentration was raised to physiological levels by a bolus injection of unlabelled rat HDL, both the serum decay and the tissue uptake of apo A-I labelled HDL were almost completely restored to conditions encountered in control animals. In vitro binding experiments showed that liver membranes obtained from EE-treated rats demonstrated a 6-fold increased specific binding of human 125I-LDL, but virtually unchanged specific binding of rat 125I-HDL, as compared with liver membranes obtained from control rats. It is concluded that rat HDL apo A-I catabolism is hardly mediated by the apo B/E receptor induced by EE treatment.
- Published
- 1987
- Full Text
- View/download PDF
38. Turnover and uptake by organs of radioactive serum high-density lipoprotein cholesteryl esters and phospholipids in the rat in vivo.
- Author
-
Van't Hooft FM, Van Gent T, and Van Tol A
- Subjects
- Animals, Cholesterol blood, Cholesterol, HDL, Half-Life, Hepatectomy, Kinetics, Male, Phosphorus Radioisotopes, Rats, Tissue Distribution, Tritium, Cholesterol Esters blood, Lipoproteins, HDL blood, Phospholipids blood
- Abstract
The serum decay of rat serum high-density lipoprotein (HD lipoprotein), labelled biosynthetically with (32)P in the phospholipid or with (3)H in the cholesteryl ester moiety, was measured in rats after partial hepatectomy or sham operation. The serum decay of (3)H-labelled HD lipoprotein cholesteryl esters was biexponential. In sham-operated rats the t((1/2)) values for the rapid phase and the slow phase were 0.2+/-0.1h and 4.2+/-0.4h (means+/-s.e.m.) respectively. After removal of two-thirds of the liver the t((1/2)) value of the rapid phase did not change (0.1+/-0.1h), whereas the t((1/2)) value of the slow phase increased to 5.7+/-0.8h. Partial hepatectomy hardly changed extrahepatic tissue radioactivities, whereas the percentage of the injected dose recovered in the liver 6h after injection decreased from 34.0+/-1.9% before to 13.5+/-1.6% after partial hepatectomy. The (32)P-labelled HD lipoprotein phospholipids showed a rapid monoexponential decay from serum with t((1/2)) values of 0.71+/-0.3h and 1.48+/-0.11h after sham operation or partial hepatectomy respectively. The tissue (32)P radioactivities in the shamoperated rats, measured 1h after injection, were 46.0+/-1.7% (liver), 1.7+/-0.3% (adipose tissue), 3.7+/-1.2% (skeletal muscle) and 3.0+/-0.0% (erythrocytes) of the injected dose. Only the value for liver was affected by partial hepatectomy and decreased to 16.7+/-3.8%. In a previous publication [Van Tol, Van Gent, Van't Hooft & Vlaspolder (1978) Atherosclerosis29, 439-448] we showed in a highly comparable experimental setting that the turnover rates of HD apolipoproteins A and C in vivo are not influenced by removal of two-thirds of the liver. From the present study it is clear that the removal rates of radioactive HD lipoprotein cholesteryl esters and HD lipoprotein phospholipids from serum in vivo are decreased by partial hepatectomy. The results indicate the possibility of partly separate metabolic pathways of HD apolipoproteins A and C, HD lipoprotein cholesteryl esters and HD lipoprotein phospholipids. The phospholipids and cholesteryl esters of HD lipoprotein are metabolized predominantly by the liver. Possible mechanisms for the hepatic uptake and metabolism of HD lipoprotein cholesteryl (esters) and phospholipids are discussed.
- Published
- 1981
- Full Text
- View/download PDF
39. Pathological laughing.
- Author
-
SILLEVIS SMITT WG and VAN'T HOOFT F
- Subjects
- Humans, Diencephalon, Disease, Laughter
- Published
- 1953
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