213 results on '"Skorpen, F."'
Search Results
2. Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients
- Author
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Colombo, F, Pintarelli, G, Galvan, A, Noci, S, Corli, O, Skorpen, F, Klepstad, P, Kaasa, S, Pigni, A, Brunelli, C, Roberto, A, Piazza, R, Pirola, A, Gambacorti Passerini, C, Caraceni, A, Colombo F., Pintarelli G., Galvan A., Noci S., Corli O., Skorpen F., Klepstad P., Kaasa S., Pigni A., Brunelli C., Roberto A., Piazza R., Pirola A., Gambacorti Passerini C., Caraceni A. T., Colombo, F, Pintarelli, G, Galvan, A, Noci, S, Corli, O, Skorpen, F, Klepstad, P, Kaasa, S, Pigni, A, Brunelli, C, Roberto, A, Piazza, R, Pirola, A, Gambacorti Passerini, C, Caraceni, A, Colombo F., Pintarelli G., Galvan A., Noci S., Corli O., Skorpen F., Klepstad P., Kaasa S., Pigni A., Brunelli C., Roberto A., Piazza R., Pirola A., Gambacorti Passerini C., and Caraceni A. T.
- Abstract
Nausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of DNA pools from patients with either low (n = 937) or high (n = 557) nausea and vomiting intensity, recruited in the European Pharmacogenetic Opioid Study, revealed a preliminary association of 53 polymorphisms. PCR-based genotyping of 45 of these polymorphisms in the individual patients of the same series confirmed the association for six SNPs in AIM1L, CLCC1, MUC16, PDE3A, POM121L2, and ZNF165 genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in ZNF568 and PDE3A genes. Only one SNP, rs12305038 in PDE3A, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak.
- Published
- 2020
3. Influence from genetic variability on opioid use for cancer pain: A European genetic association study of 2294 cancer pain patients
- Author
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Klepstad, P., Fladvad, T., Skorpen, F., Bjordal, K., Caraceni, A., Dale, O., Davies, A., Kloke, M., Lundström, S., Maltoni, M., Radbruch, L., Sabatowski, R., Sigurdardottir, V., Strasser, F., Fayers, P.M., and Kaasa, S.
- Published
- 2011
- Full Text
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4. Genetic clustering of European cancer patients indicates that opioid-mediated pain relief is independent of ancestry
- Author
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Galvan, A, Fladvad, T, Skorpen, F, Gao, X, Klepstad, P, Kaasa, S, and Dragani, T A
- Published
- 2012
- Full Text
- View/download PDF
5. Time dynamics of autoantibodies are coupled to phenotypes and add to the heterogeneity of autoimmune diabetes in adults: the HUNT study, Norway
- Author
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Sørgjerd, E. P., Skorpen, F., Kvaløy, K., Midthjell, K., and Grill, V.
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- 2012
- Full Text
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6. The association between headache and Val158Met polymorphism in the catechol–O–methyltransferase gene: the HUNT Study
- Author
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Hagen, K., Pettersen, E., Stovner, L. J., Skorpen, F., and Zwart, J.-A.
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- 2006
- Full Text
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7. The causal role of smoking in anxiety and depression: a Mendelian randomization analysis of the HUNT study
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Bjørngaard, J. H., Gunnell, D., Elvestad, M. B., Smith, G. Davey, Skorpen, F., Krokan, H., Vatten, L., and Romundstad, P.
- Published
- 2013
8. Nociceptive stimuli responses at different levels of general anaesthesia and genetic variability
- Author
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Storm, H., Sten, R., Klepstad, P., Skorpen, F., Qvigstad, E., and Ræder, J.
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- 2013
- Full Text
- View/download PDF
9. MULTIPLE LOCI MODULATE OPIOID THERAPY RESPONSE FOR CANCER PAIN: PP123
- Author
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Galvan, A., Skorpen, F., Klepstad, P., Knudsen, A. K., Fladvad, T., Falvella, F. S., Pigni, A., Brunelli, C., Caraceni, A., Kaasa, S., and Dragani, T.
- Published
- 2012
10. A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2)
- Author
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Roten, L.T., Fenstad, M.H., Forsmo, S., Johnson, M.P., Moses, E.K., Austgulen, R., and Skorpen, F.
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- 2011
- Full Text
- View/download PDF
11. Variable response to opioid treatment: any genetic predictors within sight?
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Skorpen, F, Laugsand, E A, Klepstad, P, and Kaasa, S
- Published
- 2008
12. Variable response to opioid treatment: genetic predictors within sight?: IL1E-6
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Skorpen, F.
- Published
- 2008
13. Genetic variability and clinical efficacy of morphine
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KLEPSTAD, P., DALE, O., SKORPEN, F., BORCHGREVINK, P. C., and KAASA, S.
- Published
- 2005
14. The 118 A > G polymorphism in the human μ-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease
- Author
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KLEPSTAD, P., RAKVÅG, T. T., KAASA, S., HOLTHE, M., DALE, O., BORCHGREVINK, P. C., BAAR, C., VIKAN, T., KROKAN, H. E., and SKORPEN, F.
- Published
- 2004
15. Sequence variations in the UDP-glucuronosyltransferase 2B7 (UGT2B7) gene: identification of 10 novel single nucleotide polymorphisms (SNPs) and analysis of their relevance to morphine glucuronidation in cancer patients
- Author
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Holthe, M, Rakvåg, T N, Klepstad, P, Idle, J R, Kaasa, S, Krokan, H E, and Skorpen, F
- Published
- 2003
16. New genetic loci link adipose and insulin biology to body fat distribution
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Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, Cooper, R, Dedoussis, G, Ferrucci, L, Froguel, P, Grabe, H, Hamsten, A, Hui, J, Hveem, K, Jöckel, K, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, März, W, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Pe'Russe, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sinisalo, J, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, Van Der Harst, P, Veronesi, G, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Abecasis, G, Assimes, T, Berndt, S, Boehnke, M, Borecki, I, Deloukas, P, Franke, L, Frayling, T, Groop, L, Hunter, D, Kaplan, R, O'Connell, J, Qi, L, Schlessinger, D, Strachan, D, Stefansson, K, Van Duijn, C, Willer, C, Visscher, P, Yang, J, Hirschhorn, J, Zillikens, M, Mccarthy, M, Speliotes, E, North, K, Fox, C, Barroso, I, Franks, P, Ingelsson, E, Heid, I, Loos, R, Cupples, L, Lindgren, C, Mohlke, K, Dastani, Z, Timpson, N, Yuan, X, Henneman, P, Kizer, J, Lyytikainen, L, Fuchsberger, C, Small, K, Coassin, S, Lohman, K, Pankow, J, Uh, H, Wu, Y, Bidulescu, A, Rasmussen Torvik, L, Greenwood, C, Ladouceur, M, Grimsby, J, Manning, A, Mooser, V, Kapur, K, Frants, R, Willemsvan vanDijk, K, Willems, S, Psaty, B, Tracy, R, Brody, J, Chen, I, Viikari, J, Kähönen, M, Evans, D, St Pourcain, B, Sattar, N, Carlson, O, Egan, J, van Heemst, D, Kedenko, L, Nuotio, M, Loo, B, Kanaya, A, Haun, M, Klopp, N, Katsareli, E, Couper, D, Duncan, B, Kloppenburg, M, Borja, J, Musani, S, Guo, X, Semple, R, Teslovich, T, Allison, M, Redline, S, Buxbaum, S, Meulenbelt, I, Ballantyne, C, Hu, F, Paulweber, B, Florez, J, Smith, G, Siscovick, D, Kronenberg, F, van Duijn, C, Waterworth, D, Meigs, J, Dupuis, J, Richards, J, Willenborg, C, Thompson, J, Erdmann, J, Goldstein, B, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikäinen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Cox, D, Dimitriou, M, 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, Peden, J, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Basart, H, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Goodall, A, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kim, H, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Hovingh, G, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Kathiresan, S, Roberts, R, Schunkert, H, Pattaro, C, Köttgen, A, Garnaas, M, Böger, C, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Gorski, M, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Trompet, S, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Döring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Wright, A, Ellinghaus, D, Nöthlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Völzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Krämer, B, Portas, L, Ford, I, Buckley, B, Adam, M, Thun, G, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Gasparini, P, Pirastu, M, Jukema, J, Probst Hensch, N, Toniolo, D, Coresh, J, Schmidt, R, Kardia, S, Curhan, G, Gyllensten, U, Franke, A, Rettig, R, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, van der Harst, P, Arking, D, Franceschini, N, Hernandez, D, Townsend, R, Lumley, T, Kestenbaum, B, Haritunians, T, Waeber, G, Lu, X, Leak, T, Aasarød, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Beckmann, J, Dreisbach, A, Styrkarsdottir, U, Evangelou, E, Hsu, Y, Duncan, E, Ntzani, E, Oei, L, Albagha, O, Kemp, J, Koller, D, Minster, R, Vandenput, L, Willner, D, Xiao, S, Yerges Armstrong, L, Zheng, H, Alonso, N, Kammerer, C, Kaptoge, S, Leo, P, Wilson, S, Aalto, V, Alen, M, Aragaki, A, Center, J, Dailiana, Z, Duggan, D, Garcia Giralt, N, Giroux, S, Hocking, L, Husted, L, Jameson, K, Khusainova, R, Kim, G, Koromila, T, Kruk, M, Laaksonen, M, Lacroix, A, Lee, S, Leung, P, Lewis, J, Masi, L, Mencej 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- Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
- Published
- 2015
17. Genetic studies of body mass index yield new insights for obesity biology
- Author
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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. 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- 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.
- Published
- 2015
18. The causal role of smoking on the risk of headache. A Mendelian randomization analysis in the HUNT study
- Author
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Johnsen, M. B., primary, Winsvold, B. S., additional, Børte, S., additional, Vie, G. Å., additional, Pedersen, L. M., additional, Storheim, K., additional, Skorpen, F., additional, Hagen, K., additional, Bjørngaard, J. H., additional, Åsvold, B. O., additional, and Zwart, J. A., additional
- Published
- 2018
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19. Lung cancer susceptibility locus at 5p15.33
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McKay JD, Hung RJ, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, Zaridze D, Mukeria A, Szeszenia Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, McLaughlin J, Shepherd F, Montpetit A, Narod S, Krokan HE, Skorpen F, Elvestad MB, Vatten L, Njølstad I, Axelsson T, Chen C, Goodman G, Barnett M, Loomis MM, Lubiñski J, Matyjasik J, Lener M, Oszutowska D, Field J, Liloglou T, Xinarianos G, Cassidy A, EPIC Study, Vineis P, Clavel Chapelon F, Palli D, Tumino R, Krogh V, González CA, Ramón Quirós J, Martínez C, Navarro C, Ardanaz E, Larrañaga N, Kham KT, Key T, Bueno de Mesquita HB, Peeters PH, Trichopoulou A, Linseisen J, Boeing H, Hallmans G, Overvad K, Tjønneland A, Kumle M, Riboli E, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P., PANICO, SALVATORE, McKay, J.D., Hung, R.J., Gaborieau, V., Boffetta, P., Chabrier, A., Byrnes, G., Zaridze, D., Mukeria, A., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Bencko, V., Foretova, L., Janout, V., McLaughlin, J., Shepherd, F., Montpetit, A., Narod, S., Krokan, H.E., Skorpen, F., Elvestad, M.B., Vatten, L., Njølstad, I., Axelsson, T., Chen, C., Goodman, G., Barnett, M., Loomis, M.M., Lubiski, J., Matyjasik, J., Lener, M., Oszutowska, D., Field, J., Liloglou, T., Xinarianos, G., Cassidy, A., Zelenika, D., Boland, A., Delepine, M., Foglio, M., Lechner, D., Matsuda, F., Blanche, H., Gut, I., Heath, S., Lathrop, M., Brennan, P., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., González, C.A., Ramón Quirós, J., Martínez, C., Navarro, C., Ardanaz, E., Larrãaga, N., Kham, K.T., Key, T., Bueno-De-Mesquita, H.B., Peeters, P.H.M., Trichopoulou, A., Linseisen, J., Boeing, H., Hallmans, G., Overvad, K., Tjønneland, A., Kumle, M., Riboli, E., Mckay, Jd, Hung, Rj, Gaborieau, V, Boffetta, P, Chabrier, A, Byrnes, G, Zaridze, D, Mukeria, A, Szeszenia Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Mates, D, Bencko, V, Foretova, L, Janout, V, Mclaughlin, J, Shepherd, F, Montpetit, A, Narod, S, Krokan, He, Skorpen, F, Elvestad, Mb, Vatten, L, Njølstad, I, Axelsson, T, Chen, C, Goodman, G, Barnett, M, Loomis, Mm, Lubiñski, J, Matyjasik, J, Lener, M, Oszutowska, D, Field, J, Liloglou, T, Xinarianos, G, Cassidy, A, Epic, Study, Vineis, P, Clavel Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, Salvatore, González, Ca, Ramón Quirós, J, Martínez, C, Navarro, C, Ardanaz, E, Larrañaga, N, Kham, Kt, Key, T, Bueno de Mesquita, Hb, Peeters, Ph, Trichopoulou, A, Linseisen, J, Boeing, H, Hallmans, G, Overvad, K, Tjønneland, A, Kumle, M, Riboli, E, Zelenika, D, Boland, A, Delepine, M, Foglio, M, Lechner, D, Matsuda, F, Blanche, H, Gut, I, Heath, S, and Lathrop, M
- Subjects
Lung Neoplasms ,Locus (genetics) ,Genome-wide association study ,Apoptosis ,Biology ,Article ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Lung cancer ,Gene ,Telomerase ,Principal Component Analysis ,Respiratory disease ,Smoking ,Case-control study ,Cancer ,Membrane Proteins ,medicine.disease ,Lung cancer susceptibility ,Molecular biology ,Neoplasm Proteins ,Case-Control Studies ,Immunology ,Chromosomes, Human, Pair 5 ,Genome-Wide Association Study - Abstract
We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 × 10-7 and P = 4 × 10-6) and replicated by the independent study series (P = 7 × 10-5 and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology. © 2008 Nature Publishing Group.
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- 2008
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20. Erratum: Sequence variations in the UDP-glucuronosyltransferase 2B7 (UGT2B7) gene: identification of 10 novel single nucleotide polymorphisms (SNPs) and analysis of their relevance to morphine glucuronidation in cancer patients
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Holthe, M, Rakvág, T N, Klepstad, P, Idle, J R, Kaasa, S, Krokan, H E, and Skorpen, F
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- 2003
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21. The causal role of smoking on the risk of hip or knee replacement due to primary osteoarthritis. a mendelian randomization analysis of the nord-trØndelag health study
- Author
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Johnsen, M.B., primary, Vie, G.Å., additional, Winsvold, B.S., additional, Bjørngaard, J.H., additional, Åsvold, B.O., additional, Gabrielsen, M.E., additional, Pedersen, L.M., additional, Hellevik, A.I., additional, Langhammer, A., additional, Furnes, O., additional, Flugsrud, G.B., additional, Skorpen, F., additional, Romundstad, P.R., additional, Storheim, K., additional, Nordsletten, L., additional, and Zwart, J.A., additional
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- 2017
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22. Genetic variations and cognitive dysfunction in opioid treated patients with cancer
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Kurita, GP, Ekholm, Ola, Kaasa, S, Klepstad, P, Skorpen, F, and Sjøgren, P
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- 2015
23. The rare Arg181Cys mutation in the μ opioid receptor can abolish opioid responses
- Author
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Skorpen, F., primary, von Hofacker, S., additional, Bjørngaard, M., additional, Skogholt, A. H., additional, Dale, O., additional, Kaasa, S., additional, and Klepstad, P., additional
- Published
- 2016
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24. New genetic loci link adipose and insulin biology to body fat distribution.
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ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., Carlson, OD., Egan, JM., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, ML., Loo, BM., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, HE., Deloukas, P., Katsareli, E., Couper, DJ., Duncan, BB., Kloppenburg, M., Adair, LS., Borja, JB., Wilson, JG., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, TM., Allison, MA., Redline, S., Buxbaum, SG., Mohlke, KL., Meulenbelt, I., Ballantyne, CM., Dedoussis, GV., Hu, FB., Liu, Y., Paulweber, B., Spector, TD., Slagboom, P., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, JC., Salomaa, V., Eriksson, JG., Frayling, TM., Hicks, AA., Lehtimäki, T., Smith, GD., Siscovick, DS., Kronenberg, F., van Duijn, C., Loos, RJ., Waterworth, DM., Meigs, JB., Dupuis, J., Richards, JB., Willenborg, C., Farrall, M., Assimes, TL., Thompson, JR., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, BA., Stirrups, K., König, IR., Cazier, JB., Johansson£££Åsa£££ Å., Hall, AS., Lee, JY., Willer, CJ., Chambers, JC., 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NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Winkler, T.W., Croteau-Chonka, D.C., Locke, A.E., Strawbridge, R.J., Pers, T.H., Justice, A.E., Workalemahu, T., Wu, J.M., Buchkovich, M.L., Heard-Costa, N.L., Roman, T.S., Drong, A.W., Day, F.R., Luan, J., Randall, J.C., Scherag, A., Wood, A.R., Fehrmann, R., Karjalainen, J., Kahali, B., Liu, C.T., Schmidt, E.M., Anderson, D., Bragg-Gresham, J.L., Ehret, G.B., Feitosa, M.F., Jackson, A.U., Kleber, M.E., Mateo Leach, I., Medina-Gomez, C., Palmer, C.D., Pasko, D., Pechlivanis, S., Peters, M.J., Ju Sung, Y., Van Vliet-Ostaptchouk, J.V., Yengo, L., Arscott, G.M., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bonnet, F., Böttcher, Y., Carba, D.B., Caspersen, I.H., Daw, E.W., Deelen, J., Delgado, G., Doney, A.S., Eklund, N., Erdos, M.R., Eury, E., Friedrich, N., Garcia, M.E., Giedraitis, V., Go, A.S., Golay, A., Grammer, T.B., Gräßler, J., 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J.A., Steinthorsdottir, V., Stolk, R.P., Strauch, K., Tremblay, A., Vohl, M.C., Wilson, J.F., Witteman, J.C., Adair, L.S., Boehm, B.O., Bornstein, S.R., Bouchard, C., Cauchi, S., Caulfield, M.J., Chambers, J.C., Chasman, D.I., Cooper, R.S., Grabe, H.J., Jöckel, K.H., Munroe, P.B., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Pérusse, L., Saaristo, T.E., Slagboom, P.E., Spector, T.D., Uitterlinden, A.G., Veronesi, G., Walker, M., Wareham, N.J., Wichmann, H.E., Abecasis, G.R., Assimes, T.L., Berndt, S.I., Borecki, I.B., Frayling, T.M., Groop, L.C., Hunter, D.J., Kaplan, R.C., O'Connell, J.R., Strachan, D.P., van Duijn, C.M., Willer, C.J., Visscher, P.M., Yang, J., Hirschhorn, J.N., Zillikens, M.C., McCarthy, M.I., Speliotes, E.K., North, K.E., Fox, C.S., Franks, P.W., Heid, I.M., Loos, R.J., Cupples, L.A., Morris, A.P., Lindgren, C.M., and Mohlke, K.L.
- Abstract
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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- 2015
25. The causal role of smoking on the risk of headache. A Mendelian randomization analysis in the HUNT study.
- Author
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Børte, S., Johnsen, M. B., Zwart, J. A., Pedersen, L. M., Storheim, K., Winsvold, B. S., Åsvold, B. O., Vie, G. Å., Bjørngaard, J. H., Skorpen, F., and Hagen, K.
- Subjects
SMOKING ,RANDOMIZATION (Statistics) ,HEADACHE ,EPIDEMIOLOGY ,SINGLE nucleotide polymorphisms ,GENOTYPES ,MIGRAINE - Abstract
Background and purpose: Headache has been associated with various lifestyle and psychosocial factors, one of which is smoking. The aim of the present study was to investigate whether the association between smoking intensity and headache is likely to be causal. Method: A total of 58 316 participants from the Nord‐Trøndelag Health (HUNT) study with information on headache status were genotyped for the rs1051730 C>T single‐nucleotide polymorphism (SNP). The SNP was used as an instrument for smoking intensity in a Mendelian randomization analysis. The association between rs1051730 T alleles and headache was estimated by odds ratios with 95% confidence intervals. Additionally, the association between the SNP and migraine or non‐migrainous headache versus no headache was investigated. All analyses were adjusted for age and sex. Results: There was no strong evidence that the rs1051730 T allele was associated with headache in ever smokers (odds ratio 0.99, 95% confidence interval 0.95–1.02). Similarly, there was no association between the rs1051730 T allele and migraine or non‐migrainous headache versus no headache. Conclusion: The findings from this study do not support that there is a strong causal relationship between smoking intensity and any type of headache. Larger Mendelian randomization studies are required to examine whether higher smoking quantity can lead to a moderate increase in the risk of headache subtypes. [ABSTRACT FROM AUTHOR]
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- 2018
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26. MON-PP096: Changes in Plasma Levels of Omega-3 Pufas in Response to Supplementation with Omega-3 Pufa-Enriched Oral Nutritional Supplements in Advanced Cancer Patients
- Author
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Balstad, T.R., primary, Pettersen, C.H., additional, Laird, B., additional, Fearon, K., additional, Schønberg, S.M.A., additional, Skorpen, F., additional, Kaasa, S., additional, Solheim, T.S., additional, and Bye, A., additional
- Published
- 2015
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27. Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: The CARTA consortium
- Author
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Taylor, A.E. (Amy E.), Fluharty, M.E. (Meg E.), Bjørngaard, J.H. (Johan H.), Gabrielsen, M.E. (Maiken Elvestad), Skorpen, F. (Frank), Marioni, R.E. (Riccardo), Campbell, A. (Archie), Engmann, J. (Jorgen), Mirza, S.S. (Saira), Loukola, A. (Anu), Laatikainen, T. (Tiina), Partonen, T. (Timo), Kaakinen, M. (Marika), Ducci, F. (Francesca), Cavadino, A. (Alana), Husemoen, L.L.N. (Lise Lotte), Ahluwalia, T.S. (Tarunveer Singh), Jacobsen, R.K. (Rikke Kart), Skaaby, T. (Tea), Ebstrup, J.F. (Jeanette Frost), Mortensen, E.L. (Erik), Minica, C.C. (Camelia C.), Vink, J.M. (Jacqueline), Willemsen, G.A.H.M. (Gonneke), Marques-Vidal, P. (Pedro), Dale, C.E. (Caroline E.), Amuzu, A. (Antoinette), Lennon, L.T. (Lucy T.), Lahti, J. (Jari), Palotie, A. (Aarno), Räikkönen, K. (Katri), Wong, A. (Andrew), Paternoster, L. (Lavinia), Wong, A.P.-Y. (Angelita Pui-Yee), Horwood, L.J. (L. John), Murphy, M. (Michael), Johnstone, E.C. (Elaine C.), Kennedy, M.A. (Martin A.), Pausova, Z. (Zdenka), Paus, T. (Tomáš), Ben-Shlomo, Y., Nohr, C. (Christian), Kuh, D. (Diana), Kivimaki, M. (Mika), Eriksson, J.G. (Johan G.), Morris, R.W. (Richard), Casas, J.P. (Juan), Preisig, M. (Martin), Boomsma, D.I. (Dorret), Linneberg, A. (Allan), Power, C. (Christopher), Hypponen, E. (Elina), Veijola, J. (Juha), Jarvelin, M.-R. (Marjo-Riitta), Korhonen, T. (Tellervo), Tiemeier, H.W. (Henning), Kumari, M. (Meena), Porteous, D.J. (David J.), Hayward, C. (Caroline), Romundstad, P.R. (Pa˚l R.), Smith, A.V. (Davey), Munafò, M.R. (Marcus), Taylor, A.E. (Amy E.), Fluharty, M.E. (Meg E.), Bjørngaard, J.H. (Johan H.), Gabrielsen, M.E. (Maiken Elvestad), Skorpen, F. (Frank), Marioni, R.E. (Riccardo), Campbell, A. (Archie), Engmann, J. (Jorgen), Mirza, S.S. (Saira), Loukola, A. (Anu), Laatikainen, T. (Tiina), Partonen, T. (Timo), Kaakinen, M. (Marika), Ducci, F. (Francesca), Cavadino, A. (Alana), Husemoen, L.L.N. (Lise Lotte), Ahluwalia, T.S. (Tarunveer Singh), Jacobsen, R.K. (Rikke Kart), Skaaby, T. (Tea), Ebstrup, J.F. (Jeanette Frost), Mortensen, E.L. (Erik), Minica, C.C. (Camelia C.), Vink, J.M. (Jacqueline), Willemsen, G.A.H.M. (Gonneke), Marques-Vidal, P. (Pedro), Dale, C.E. (Caroline E.), Amuzu, A. (Antoinette), Lennon, L.T. (Lucy T.), Lahti, J. (Jari), Palotie, A. (Aarno), Räikkönen, K. (Katri), Wong, A. (Andrew), Paternoster, L. (Lavinia), Wong, A.P.-Y. (Angelita Pui-Yee), Horwood, L.J. (L. John), Murphy, M. (Michael), Johnstone, E.C. (Elaine C.), Kennedy, M.A. (Martin A.), Pausova, Z. (Zdenka), Paus, T. (Tomáš), Ben-Shlomo, Y., Nohr, C. (Christian), Kuh, D. (Diana), Kivimaki, M. (Mika), Eriksson, J.G. (Johan G.), Morris, R.W. (Richard), Casas, J.P. (Juan), Preisig, M. (Martin), Boomsma, D.I. (Dorret), Linneberg, A. (Allan), Power, C. (Christopher), Hypponen, E. (Elina), Veijola, J. (Juha), Jarvelin, M.-R. (Marjo-Riitta), Korhonen, T. (Tellervo), Tiemeier, H.W. (Henning), Kumari, M. (Meena), Porteous, D.J. (David J.), Hayward, C. (Caroline), Romundstad, P.R. (Pa˚l R.), Smith, A.V. (Davey), and Munafò, M.R. (Marcus)
- Abstract
Objectives: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. Participants: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). Primary outcome measures: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. Results: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. Conclusions: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the develop
- Published
- 2014
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28. Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium
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Taylor, A.E., Fluharty, M.E., Björngaard, J.H., Gabrielsen, M.E., Skorpen, F., Marioni, R.E., Campbell, A., Engmann, J., Mirza, S.S., Loukola, A., Laatikainen, T., Partonen, T., Kaakinen, M., Ducci, F., Cavadino, A., Husemoen, L.L.N., Ahluwalia, T.V.S., Jacobsen, R.K., Skaaby, T., Ebstrup, J.F., Mortensen, E.L., Minica, C.C., Vink, J.M., Willemsen, G., Marques-Vidal, P., Dale, C.E., Amuzu, A., Lennon, L.T., Lahti, J., Palotie, A., Raikkonen, K., Wong, A., Paternoster, L., Wong, A.P.Y, Horwood, L.J., Murphy, M., Johnstone, E.C., Kennedy, M.A., Pausova, Z., Paus, T., Ben-Shlomo, Y., Nohr, E.A., Kuh, D., Kivimäki, M., Eriksson, J.G., Morris, R.W., Casas, J.P., Preisig, M., Boomsma, D.I., Linneberg, A., Power, C., Hypponen, E., Veijola, J., Jarvelin, M.R., Korhonen, T., Tiemeier, H., Kumari, M., Porteous, D.J., Hayward, C., Romundstad, P.R., Smith, G.D., Munafò, M.R., Taylor, A.E., Fluharty, M.E., Björngaard, J.H., Gabrielsen, M.E., Skorpen, F., Marioni, R.E., Campbell, A., Engmann, J., Mirza, S.S., Loukola, A., Laatikainen, T., Partonen, T., Kaakinen, M., Ducci, F., Cavadino, A., Husemoen, L.L.N., Ahluwalia, T.V.S., Jacobsen, R.K., Skaaby, T., Ebstrup, J.F., Mortensen, E.L., Minica, C.C., Vink, J.M., Willemsen, G., Marques-Vidal, P., Dale, C.E., Amuzu, A., Lennon, L.T., Lahti, J., Palotie, A., Raikkonen, K., Wong, A., Paternoster, L., Wong, A.P.Y, Horwood, L.J., Murphy, M., Johnstone, E.C., Kennedy, M.A., Pausova, Z., Paus, T., Ben-Shlomo, Y., Nohr, E.A., Kuh, D., Kivimäki, M., Eriksson, J.G., Morris, R.W., Casas, J.P., Preisig, M., Boomsma, D.I., Linneberg, A., Power, C., Hypponen, E., Veijola, J., Jarvelin, M.R., Korhonen, T., Tiemeier, H., Kumari, M., Porteous, D.J., Hayward, C., Romundstad, P.R., Smith, G.D., and Munafò, M.R.
- Abstract
Contains fulltext : 160020.pdf (publisher's version ) (Open Access), Objectives: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. Participants: Current, former and never smokers of European ancestry aged >= 16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). Primary outcome measures: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. Results: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR= 1.02, 95% CI 0.97 to 1.07) or psychological distress (OR= 1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. Conclusions: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the dev
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- 2014
29. Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium
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Taylor, AE, Fluharty, ME, Bjorngaard, JH, Gabrielsen, ME, Skorpen, F, Marioni, RE, Campbell, A (Archie), Engmann, J, Mirza, Saira, Loukola, A, Laatikainen, T, Partonen, T, Kaakinen, M, Ducci, F, Cavadino, A, Husemoen, LLN, Ahluwalia, TS, Jacobsen, RK, Skaaby, T, Ebstrup, JF, Mortensen, EL, Minica, CC, Vink, JM, Willemsen, G, Marques-Vidal, P, Dale, CE, Amuzu, A, Lennon, LT, Lahti, J, Palotie, A, Raikkonen, K, Wong, A, Paternoster, L, Wong, APY, Horwood, LJ, Murphy, M, Johnstone, EC, Kennedy, MA, Pausova, Z, Paus, T, Ben-Shlomo, Y, Nohr, EA, Kuh, D, Kivimaki, M, Eriksson, JG, Morris, RW, Casas, JP, Preisig, M, Boomsma, DI, Linneberg, A, Power, C, Hypponen, E, Veijola, J, Jarvelin, MR, Korhonen, T, Tiemeier, Henning, Kumari, M, Porteous, DJ, Hayward, C, Romundstad, PR, Smith, GD, Munafo, MR, Taylor, AE, Fluharty, ME, Bjorngaard, JH, Gabrielsen, ME, Skorpen, F, Marioni, RE, Campbell, A (Archie), Engmann, J, Mirza, Saira, Loukola, A, Laatikainen, T, Partonen, T, Kaakinen, M, Ducci, F, Cavadino, A, Husemoen, LLN, Ahluwalia, TS, Jacobsen, RK, Skaaby, T, Ebstrup, JF, Mortensen, EL, Minica, CC, Vink, JM, Willemsen, G, Marques-Vidal, P, Dale, CE, Amuzu, A, Lennon, LT, Lahti, J, Palotie, A, Raikkonen, K, Wong, A, Paternoster, L, Wong, APY, Horwood, LJ, Murphy, M, Johnstone, EC, Kennedy, MA, Pausova, Z, Paus, T, Ben-Shlomo, Y, Nohr, EA, Kuh, D, Kivimaki, M, Eriksson, JG, Morris, RW, Casas, JP, Preisig, M, Boomsma, DI, Linneberg, A, Power, C, Hypponen, E, Veijola, J, Jarvelin, MR, Korhonen, T, Tiemeier, Henning, Kumari, M, Porteous, DJ, Hayward, C, Romundstad, PR, Smith, GD, and Munafo, MR
- Abstract
Objectives: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. Participants: Current, former and never smokers of European ancestry aged >= 16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). Primary outcome measures: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. Results: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR= 1.02, 95% CI 0.97 to 1.07) or psychological distress (OR= 1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. Conclusions: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the dev
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- 2014
30. Lung cancer susceptibility locus at 5p15.33
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McKay, J.D. Hung, R.J. Gaborieau, V. Boffetta, P. Chabrier, A. Byrnes, G. Zaridze, D. Mukeria, A. Szeszenia-Dabrowska, N. Lissowska, J. Rudnai, P. Fabianova, E. Mates, D. Bencko, V. Foretova, L. Janout, V. McLaughlin, J. Shepherd, F. Montpetit, A. Narod, S. Krokan, H.E. Skorpen, F. Elvestad, M.B. Vatten, L. Njølstad, I. Axelsson, T. Chen, C. Goodman, G. Barnett, M. Loomis, M.M. Lubĩski, J. Matyjasik, J. Lener, M. Oszutowska, D. Field, J. Liloglou, T. Xinarianos, G. Cassidy, A. Zelenika, D. Boland, A. Delepine, M. Foglio, M. Lechner, D. Matsuda, F. Blanche, H. Gut, I. Heath, S. Lathrop, M. Brennan, P. Vineis, P. Clavel-Chapelon, F. Palli, D. Tumino, R. Krogh, V. Panico, S. González, C.A. Ramón Quirós, J. Martínez, C. Navarro, C. Ardanaz, E. Larrãaga, N. Kham, K.T. Key, T. Bueno-De-Mesquita, H.B. Peeters, P.H.M. Trichopoulou, A. Linseisen, J. Boeing, H. Hallmans, G. Overvad, K. Tjønneland, A. Kumle, M. Riboli, E.
- Abstract
We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 × 10-7 and P = 4 × 10-6) and replicated by the independent study series (P = 7 × 10-5 and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology. © 2008 Nature Publishing Group.
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- 2008
31. No large-effect low-frequency coding variation found for myocardial infarction
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Holmen, O. L., primary, Zhang, H., additional, Zhou, W., additional, Schmidt, E., additional, Hovelson, D. H., additional, Langhammer, A., additional, Lochen, M.-L., additional, Ganesh, S. K., additional, Mathiesen, E. B., additional, Vatten, L., additional, Platou, C., additional, Wilsgaard, T., additional, Chen, J., additional, Skorpen, F., additional, Dalen, H., additional, Boehnke, M., additional, Abecasis, G. R., additional, Njolstad, I., additional, Hveem, K., additional, and Willer, C. J., additional
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- 2014
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32. Influence from genetic variability on opioid use for cancer pain: a European genetic association study of 2294 cancer pain patients
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Klepstad, P, Fladvad, T, Skorpen, F, Bjordal, K, Caraceni, A, Dale, O, Davies, A, Kloke, M, Lundström, S, Maltoni, M, Radbruch, L, Sabatowski, R, Sigurdardottir, V, Strasser, F, Fayers, P M, Kaasa, S, Sjøgren, Per, Klepstad, P, Fladvad, T, Skorpen, F, Bjordal, K, Caraceni, A, Dale, O, Davies, A, Kloke, M, Lundström, S, Maltoni, M, Radbruch, L, Sabatowski, R, Sigurdardottir, V, Strasser, F, Fayers, P M, Kaasa, S, and Sjøgren, Per
- Abstract
Cancer pain patients need variable opioid doses. Preclinical and clinical studies suggest that opioid efficacy is related to genetic variability. However, the studies have small samples, findings are not replicated, and several candidate genes have not been studied. Therefore, a study of genetic variability with opioid doses in a large population using a confirmatory validation population was warranted. We recruited 2294 adult European patients using a World Health Organization (WHO) step III opioid and analyzed single nucleotide polymorphisms (SNPs) in genes with a putative influence on opioid mechanisms. The patients' mean age was 62.5 years, and the average pain intensity was 3.5. The patients' primary opioids were morphine (n=830), oxycodone (n=446), fentanyl (n=699), or other opioids (n=234). Pain intensity, time on opioids, age, gender, performance status, and bone or CNS metastases predicted opioid dose and were included as covariates. The patients were randomly divided into 1 development sample and 1 validation sample. None of 112 SNPs in the 25 candidate genes OPRM1, OPRD1, OPRK1, ARRB2, GNAZ, HINT1, Stat6, ABCB1, COMT, HRH1, ADRA2A, MC1R, TACR1, GCH1, DRD2, DRD3, HTR3A, HTR3B, HTR2A, HTR3C, HTR3D, HTR3E, HTR1, or CNR1 showed significant associations with opioid dose in both the development and the validation analyzes. These findings do not support the use of pharmacogenetic analyses for the assessed SNPs to guide opioid treatment. The study also demonstrates the importance of validating findings obtained in genetic association studies to avoid reporting spurious associations as valid findings. To elicit knowledge about new genes that influence pain and the need for opioids, strategies other than the candidate gene approach is needed.
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- 2011
33. A low COMT activity haplotype is associated with recurrent preeclampsia in a Norwegian population cohort (HUNT2)
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Roten, L., Fenstad, M., Forsmo, S., Johnson, M., Moses, Eric, Austgulen, R., Skorpen, F., Roten, L., Fenstad, M., Forsmo, S., Johnson, M., Moses, Eric, Austgulen, R., and Skorpen, F.
- Abstract
The etiology of preeclampsia is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. Although many candidate genes for preeclampsia have been suggested and studied, the specific causative genes still remain to be identified. Catechol-O-methyltransferase (COMT) is an enzyme involved in catecholamine and estrogen degradation and has recently been ascribed a role in development of preeclampsia. In the present study, we have examined the COMT gene by genotyping the functional Val108/158Met polymorphism (rs4680) and an additional single-nucleotide polymorphism, rs6269, predicting COMT activity haplotypes in a large Norwegian case/control cohort (ncases= 1135, ncontrols= 2262). A low COMT activity haplotype is associated with recurrent preeclampsia in our cohort. This may support the role of redox-regulated signaling and oxidative stress in preeclampsia pathogenesis as suggested by recent studies in a genetic mouse model. The COMT gene might be a genetic risk factor shared between preeclampsia and cardiovascular diseases.
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- 2011
34. Nociceptive stimuli responses at different levels of general anaesthesia and genetic variability
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STORM, H., primary, STØEN, R., additional, KLEPSTAD, P., additional, SKORPEN, F., additional, QVIGSTAD, E., additional, and RAEDER, J., additional
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- 2012
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35. The causal role of smoking in anxiety and depression: a Mendelian randomization analysis of the HUNT study
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Bjørngaard, J. H., primary, Gunnell, D., additional, Elvestad, M. B., additional, Smith, G. Davey, additional, Skorpen, F., additional, Krokan, H., additional, Vatten, L., additional, and Romundstad, P., additional
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- 2012
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36. Genetic clustering of European cancer patients indicates that opioid-mediated pain relief is independent of ancestry
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Galvan, A, primary, Fladvad, T, additional, Skorpen, F, additional, Gao, X, additional, Klepstad, P, additional, Kaasa, S, additional, and Dragani, T A, additional
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- 2011
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37. High Systolic Blood Pressure Is Associated With Val/Val Genotype in the Catechol-O-Methyltransferase GeneThe Nord-Trøndelag Health Study (HUNT)
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HAGEN, K, primary, PETTERSEN, E, additional, STOVNER, L, additional, SKORPEN, F, additional, HOLMEN, J, additional, and ZWART, J, additional
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- 2007
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38. Korleis vektlegger pasientar og personale ved psykiatriske sjukehus i Norge kva som er god omsorg?
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Skorpen, F., primary and Kristoffersen, K., additional
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- 2006
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39. The 118 A > G polymorphism in the human u-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease
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Klepstad, P., primary, Rakvag, T. T., additional, Kaasa, S., additional, Holthe, M., additional, Dale, O., additional, Borchgrevink, P. C., additional, Baar, C., additional, Vikan, T., additional, Krokan, H. E., additional, and Skorpen, F., additional
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- 2004
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40. Regulation of expression of nuclear and mitochondrial forms of human uracil-DNA glycosylase
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Haug, T., primary, Skorpen, F., additional, Aas, P. A., additional, Malm, V., additional, Skjelbred, C., additional, and Krokan, H. E., additional
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- 1998
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41. Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene
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Nilsen, H., primary, Otterlei, M., additional, Haug, T., additional, Solum, K., additional, Nagelhus, T. A., additional, Skorpen, F., additional, and Krokan, H. E., additional
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- 1997
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42. Is there a genetic cause for cancer cachexia? - a clinical validation study in 1797 patients.
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Solheim, T S, Fayers, P M, Fladvad, T, Tan, B, Skorpen, F, Fearon, K, Baracos, V E, Klepstad, P, Strasser, F, and Kaasa, S
- Subjects
CACHEXIA ,CANCER patients ,GENETIC polymorphisms ,BODY mass index ,HARDY-Weinberg formula ,DISEASES - Abstract
Background: Cachexia has major impact on cancer patients' morbidity and mortality. Future development of cachexia treatment needs methods for early identification of patients at risk. The aim of the study was to validate nine single-nucleotide polymorphisms (SNPs) previously associated with cachexia, and to explore 182 other candidate SNPs with the potential to be involved in the pathophysiology.Method: A total of 1797 cancer patients, classified as either having severe cachexia, mild cachexia or no cachexia, were genotyped.Results: After allowing for multiple testing, there was no statistically significant association between any of the SNPs analysed and the cachexia groups. However, consistent with prior reports, two SNPs from the acylpeptide hydrolase (APEH) gene showed suggestive statistical significance (P=0.02; OR, 0.78).Conclusion: This study failed to detect any significant association between any of the SNPs analysed and cachexia; although two SNPs from the APEH gene had a trend towards significance. The APEH gene encodes the enzyme APEH, postulated to be important in the endpoint of the ubiquitin system and thus the breakdown of proteins into free amino acids. In cachexia, there is an extensive breakdown of muscle proteins and an increase in the production of acute phase proteins in the liver. [ABSTRACT FROM AUTHOR]- Published
- 2011
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43. Genetic heterogeneity in latent autoimmune diabetes is linked to various degrees of autoimmune activity: results from the Nord-Trøndelag Health Study.
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Pettersen E, Skorpen F, Kvaløy K, Midthjell K, Grill V, Pettersen, Elin, Skorpen, Frank, Kvaløy, Kirsti, Midthjell, Kristian, and Grill, Valdemar
- Abstract
Objective: Previous studies have indicated that the latent autoimmune diabetes in adults (LADA) phenotype is heterogeneous and that LADA patients share features of type 1 and type 2 diabetes in various proportions. We tested for association of known type 1 and type 2 diabetes susceptibility genes in LADA subjects and analyzed relationships to a marker of autoimmune activity (titers of anti-GAD) and a phenotypic risk factor of type 2 diabetes (BMI).Research Design and Methods: Data were assembled from the Nord-Trøndelag Health Study (HUNT) study, which comprises the adult population of an entire county in Norway. We genotyped 60 single nucleotide polymorphisms (SNPs) known to be associated with type 1 or type 2 diabetes, including 14 tag SNPs used for HLA haplotyping in 120 type 1 diabetic, 126 LADA, and 1,090 type 2 diabetic patients and 1,503 age- and sex-matched nondiabetic subjects.Results: The majority of the strongly associated HLA haplotypes for type 1 diabetes were significantly associated with LADA in general, but mainly with high anti-GAD LADA patients. Two distinct HLA haplotypes were associated only with LADA and mainly in low anti-GAD LADA patients. There were no associations of non-HLA type 1 diabetes loci with LADA. Of type 2 diabetes-associated genes, the CC/CT genotypes of rs7961581 (TSPAN8) and the obesity-linked AA/AC genotypes of rs8050136 (FTO) were associated with LADA in general, but mainly in low anti-GAD LADA patients (P = 0.004 and P = 0.004, respectively).Conclusions: Genetic heterogeneity in LADA is linked to various degrees of autoimmune activity and may be partly distinct from both type 1 and type 2 diabetes. [ABSTRACT FROM AUTHOR]- Published
- 2010
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44. The 118 A > G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease.
- Author
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Klepstad, P, Rakvåg, T T, Kaasa, S, Holthe, M, Dale, O, Borchgrevink, P C, Baar, C, Vikan, T, Krokan, H E, and Skorpen, F
- Abstract
Background: Dispositions for genes encoding opioid receptors may explain some variability in morphine efficacy. Experimental studies show that morphine and morphine-6-glucuronide are less effective in individuals carrying variant alleles caused by the 118 A > G polymorphism in the mu-opioid receptor gene (OPRM1). The purpose of the study was to investigate whether this and other genetic polymorphisms in OPRM1 influence the efficacy of morphine in cancer pain patients.Methods: We screened 207 cancer pain patients on oral morphine treatment for four frequent OPRM1 gene polymorphisms. The polymorphisms were the -172 G > T polymorphism in the 5'untranslated region of exon 1, the 118 A > G polymorphism in exon 1, and the IVS2 + 31 G > A and IVS2 + 691 G > C polymorphisms, both in intron 2. Ninety-nine patients with adequately controlled pain were included in an analysis comparing morphine doses and serum concentrations of morphine and morphine metabolites in the different genotypes for the OPRM1 polymorphisms.Results: No differences related to the -172 G > T, the IVS2 + 31 G > A and the IVS2 + 691 G > C polymorphisms were observed. Patients homozygous for the variant G allele of the 118 A > G polymorphism (n = 4) needed more morphine to achieve pain control, compared to heterozygous (n = 17) and homozygous wild-type (n = 78) individuals. This difference was not explained by other factors such as duration of morphine treatment, performance status, time since diagnosis, time until death, or adverse symptoms.Conclusion: Patients homozygous for the 118 G allele of the mu-opioid receptor need higher morphine doses to achieve pain control. Thus, genetic variation at the gene encoding the mu-opioid receptor contributes to variability in patients' responses to morphine. [ABSTRACT FROM AUTHOR]- Published
- 2004
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45. The 118 A > G polymorphism in the humanµ-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease.
- Author
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Klepstad, P., Rakvag, T. T., Kaasa, S., Holthe, M., Dale, O., Borchgrevink, P. C., Baar, C., Vikan, T., Krokan, H. E., and Skorpen, F.
- Subjects
GENETIC polymorphisms ,OPIOID receptors ,MORPHINE ,NARCOTICS ,CANCER pain ,CANCER patients - Abstract
Dispositions for genes encoding opioid receptors may explain some variability in morphine efficacy. Experimental studies show that morphine and morphine-6-glucuronide are less effective in individuals carrying variant alleles caused by the 118 A > G polymorphism in theµ-opioid receptor gene (OPRM1). The purpose of the study was to investigate whether this and other genetic polymorphisms inOPRM1influence the efficacy of morphine in cancer pain patients.We screened 207 cancer pain patients on oral morphine treatment for four frequentOPRM1gene polymorphisms. The polymorphisms were the−172 G > T polymorphism in the 5′untranslated region of exon 1, the 118 A > G polymorphism in exon 1, and the IVS2 + 31 G > A and IVS2 + 691 G > C polymorphisms, both in intron 2. Ninety-nine patients with adequately controlled pain were included in an analysis comparing morphine doses and serum concentrations of morphine and morphine metabolites in the different genotypes for theOPRM1polymorphisms.No differences related to the−172 G > T, the IVS2 + 31 G > A and the IVS2 + 691 G > C polymorphisms were observed. Patients homozygous for the variant G allele of the 118 A > G polymorphism (n = 4) needed more morphine to achieve pain control, compared to heterozygous (n = 17) and homozygous wild-type (n = 78) individuals. This difference was not explained by other factors such as duration of morphine treatment, performance status, time since diagnosis, time until death, or adverse symptoms.Patients homozygous for the 118 G allele of theµ-opioid receptor need higher morphine doses to achieve pain control. Thus, genetic variation at the gene encoding theµ-opioid receptor contributes to variability in patients' responses to morphine. [ABSTRACT FROM AUTHOR]
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- 2004
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46. Evidence that changes in Se-glutathione peroxidase levels affect the sensitivity of human tumour cell lines to n-3 fatty acids.
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Schønberg, S A, Rudra, P K, Nøding, R, Skorpen, F, Bjerve, K S, and Krokan, H E
- Abstract
The human lung adenocarcinoma cell line A-427 is significantly more sensitive to cytotoxic lipid peroxidation products of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) than the human lung adenocarcinoma cell line SK-LU-1, and the glioblastoma cell lines A-172 and U-87 MG. The cytotoxic effect as well as lipid peroxidation were abolished by vitamin E. The differential sensitivities of the cell lines were not correlated to the levels of lipid peroxidation products (measured as the end product malondialdehyde), indicating differences in sensitivities to products of lipid peroxidation. The high sensitivity of A-427 is apparently due to a low level of selenium-dependent glutathione peroxidase (GSH-Px), because pretreatment with sodium selenite (250 nM) increased the GSH-Px activity 3- to 4-fold and protected the cells almost completely against the growth inhibitory effect of DHA. Furthermore, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) a seleno-organic GSH-Px mimic, suppressed the cytotoxic action of DHA to A-427 in a dose dependent manner. Northern analysis demonstrated that pretreatment with sodium selenite (250 nM) was accompanied by an increased level of GSH-Px mRNA (1.8-fold) in A-427 cells, while the level remained unchanged under the same conditions in DHA/EPA-resistant A-172 cells. In addition, the level of selenophosphate synthetase mRNA (SelD), a key intermediate in tRNA(Sec) formation, increased 1.2- to 1.7-fold in A-427 and A-172 cells after pretreatment with sodium selenite. These results indicate that upregulation of GSH-Px activity by sodium selenite in the EPA/DHA sensitive cell line A-427 may be due to an increase in mRNAs for GSH-Px and a precursor important for formation of tRNA(Sec) which is required for incorporation of selenocysteine in GSH-Px during translation. These results demonstrate an important role for GSH-Px in the cellular defence against cytotoxic lipid peroxidation products. Furthermore, measurement of GSH-Px activities in tumour cells may be one useful biochemical predictor for their sensitivities to polyunsaturated fatty acids. [ABSTRACT FROM PUBLISHER]
- Published
- 1997
47. Base excision repair of DNA in mammalian cells
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Krokan, H. E., Nilsen, H., Skorpen, F., Otterlei, M., and Slupphaug, G.
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- 2000
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48. A sequence in the N-terminal region of human uracil-DNA glycosylase with homology to XPA interacts with the C-terminal part of the 34-kDa subunit of replication protein A.
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Nagelhus, T A, Haug, T, Singh, K K, Keshav, K F, Skorpen, F, Otterlei, M, Bharati, S, Lindmo, T, Benichou, S, Benarous, R, and Krokan, H E
- Abstract
Uracil-DNA glycosylase releases free uracil from DNA and initiates base excision repair for removal of this potentially mutagenic DNA lesion. Using the yeast two-hybrid system, human uracil-DNA glycosylase encoded by the UNG gene (UNG) was found to interact with the C-terminal part of the 34-kDa subunit of replication protein A (RPA2). No interaction with RPA4 (a homolog of RPA2), RPA1, or RPA3 was observed. A sandwich enzyme-linked immunosorbent assay with trimeric RPA and the two-hybrid system both demonstrated that the interaction depends on a region in UNG localized between amino acids 28 and 79 in the open reading frame. In this part of UNG a 23-amino acid sequence has a significant homology to the RPA2-binding region of XPA, a protein involved in damage recognition in nucleotide excision repair. Trimeric RPA did not enhance the activity of UNG in vitro on single- or double-stranded DNA. A part of the N-terminal region of UNG corresponding in size to the complete presequence was efficiently removed by proteinase K, leaving the proteinase K-resistant compact catalytic domain intact and fully active. These results indicate that the N-terminal part constitutes a separate structural domain required for RPA binding and suggest a possible function for RPA in base excision repair.
- Published
- 1997
49. Evidence that changes in Se-glutathione peroxidase levels affect the sensitivity of human tumour cell lines to n-3 fatty acids.
- Author
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Schønberg, S A, Rudra, P K, Nøding, R, Skorpen, F, Bjerve, K S, and Krokan, H E
- Abstract
The human lung adenocarcinoma cell line A-427 is significantly more sensitive to cytotoxic lipid peroxidation products of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) than the human lung adenocarcinoma cell line SK-LU-1, and the glioblastoma cell lines A-172 and U-87 MG. The cytotoxic effect as well as lipid peroxidation were abolished by vitamin E. The differential sensitivities of the cell lines were not correlated to the levels of lipid peroxidation products (measured as the end product malondialdehyde), indicating differences in sensitivities to products of lipid peroxidation. The high sensitivity of A-427 is apparently due to a low level of selenium-dependent glutathione peroxidase (GSH-Px), because pretreatment with sodium selenite (250 nM) increased the GSH-Px activity 3- to 4-fold and protected the cells almost completely against the growth inhibitory effect of DHA. Furthermore, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) a seleno-organic GSH-Px mimic, suppressed the cytotoxic action of DHA to A-427 in a dose dependent manner. Northern analysis demonstrated that pretreatment with sodium selenite (250 nM) was accompanied by an increased level of GSH-Px mRNA (1.8-fold) in A-427 cells, while the level remained unchanged under the same conditions in DHA/EPA-resistant A-172 cells. In addition, the level of selenophosphate synthetase mRNA (SelD), a key intermediate in tRNA(Sec) formation, increased 1.2- to 1.7-fold in A-427 and A-172 cells after pretreatment with sodium selenite. These results indicate that upregulation of GSH-Px activity by sodium selenite in the EPA/DHA sensitive cell line A-427 may be due to an increase in mRNAs for GSH-Px and a precursor important for formation of tRNA(Sec) which is required for incorporation of selenocysteine in GSH-Px during translation. These results demonstrate an important role for GSH-Px in the cellular defence against cytotoxic lipid peroxidation products. Furthermore, measurement of GSH-Px activities in tumour cells may be one useful biochemical predictor for their sensitivities to polyunsaturated fatty acids.
- Published
- 1997
- Full Text
- View/download PDF
50. Paracetamol increases sensitivity to ultraviolet (UV) irradiation, delays repair of the UNG-gene and recovery of RNA synthesis in HaCaT cells
- Author
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Krokan, H. E., Skorpen, F., Alm, B., Skjelbred, C., and Aas, P. A.
- Published
- 1998
- Full Text
- View/download PDF
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