1. Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons
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Rotger, M, Glass, Tr, Junier, T, Lundgren, J, Neaton, Jd, Poloni, Es, van 't Wout AB, Lubomirov, R, Colombo, S, Martinez, R, Rauch, A, Günthard, Hf, Neuhaus, J, Wentworth, D, van Manen, D, Gras, La, Schuitemaker, H, Albini, L, Torti, C, Jacobson, Lp, Li, X, Kingsley, La, Carli, F, Guaraldi, G, Ford, Es, Sereti, I, Hadigan, C, Martinez, E, Arnedo, M, Egaña-Gorroño, L, Gatell, Jm, Law, M, Bendall, C, Petoumenos, K, Rockstroh, J, Wasmuth, Jc, Kabamba, K, Delforge, M, De Wit, S, Berger, F, Mauss, S, de Paz Sierra, M, Losso, M, Belloso, Wh, Leyes, M, Campins, A, Mondi, A, De Luca, A, Bernardino, I, Barriuso-Iglesias, M, Torrecilla-Rodriguez, A, Gonzalez-Garcia, J, Arribas, Jr, Fanti, I, Gel, S, Puig, J, Negredo, E, Gutierrez, M, Domingo, P, Fischer, J, Fätkenheuer, G, Alonso-Villaverde, C, Macken, A, Woo, J, Mcginty, T, Mallon, P, Mangili, A, Skinner, S, Wanke, Ca, Reiss, P, Weber, R, Bucher, Hc, Fellay, J, Telenti, A, Tarr, Pe, Vullo, V, Magnificent, Consortium, Insight, Swiss HIV Cohort Study, Mastroianni, C, MAGNIFICENT Consortium, Swiss HIV Cohort Study, INSIGHT, Rotger, M., Glass, TR., Lubomirov, R., Bucher, HC., Telenti, A., Tarr, PE., Junier, T., Poloni, ES., Fellay, J., Colombo, S., Martinez, R., Rauch, A., Weber, R., Günthard, HF., Neuhaus, J., Wentworth, D., Lundgren, J., Neaton, JD., van Manen, D., Gras, AL., Schuitemaker, H., van Wout AB., Reiss, P., Albini, L., Torti, C., Jacobson, LP., Li, X., Kingsley, LA., Carli, F., Guaraldi, G., Ford, ES., Sereti, I., Hadigan, C., Martinez, E., Arnedo-Valero, M., Egaña-Gorroño, L., Gatell, JM., Law, M., Bendall, C., Petoumenos, K., Rockstroh, J., Wasmuth, JC., Kabamba, K., Delforge, M., De Wit, S., Berger, F., Mauss, S., Sierra Mde, P., Losso, M., Belloso, WH., Leyes, M., Campins, A., Mondi, A., De Luca, A., Bernardino, I., Barriuso-Iglesias£££Mónica£££ M., Rodriguez, AT., Garcia, JG., Arribas, JR., Fanti, I., Gel, S., Puig, J., Negredo, E., Gutierrez, M., Domingo, P., Fischer, J., Fätkenheuer, G., Alonso-Villaverde, C., Macken, A., Woo, J., McGinty, T., Mallon, P., Mangili, A., Skinner, S., Wanke, CA., Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Trkola, A., Vernazza, P., Prins, YS., Kuijpers, TW., Scherpbier, HJ., Boer, K., van der Meer JT., Wit, FW., Godfried, MH., van der Poll, T., Nellen, FJ., Lange, JM., Geerlings, SE., van Vugt, M., Vrouenraets, SM., Pajkrt, D., Bos, JC., van der Valk, M., Schreij, G., Lowe, S., Lashof, AO., Pronk, MJ., Bravenboer, B., van der Ende ME., de Vries-Sluijs TE., Schurink, CA., van der Feltz, M., Nouwen, JL., Gelinck, LB., Verbon, A., Rijnders, BJ., van de Ven-de Ruiter ED., Slobbe, L., Haag, D., Kauffmann, RH., Schippers, EF., Groeneveld, PH., Alleman, MA., Bouwhuis, JW., ten Kate RW., Soetekouw, R., Kroon, FP., van den Broek PJ., van Dissel JT., Arend, SM., van Nieuwkoop, C., de Boer MJ., Jolink, H., den Hollander JG., Pogany, K., Bronsveld, W., Kortmann, W., van Twillert, G., van Houte DP., Polée, MB., van Vonderen MG., ten Napel CH., Kootstra, GJ., Brinkman, K., Blok, WL., Frissen, PH., Schouten, WE., van den Berk GE., Juttmann, JR., van Kasteren ME., Brouwer, AE., Mulder, JW., van Gorp EC., Smit, PM., Weijer, S., van Eeden, A., Verhagen, DW., Sprenger, HG., Doedens, R., Scholvinck, EH., van Assen, S., Stek, CJ., Hoepelman, IM., Mudrikova, T., Schneider, MM., Jaspers, CA., Ellerbroek, PM., Peters, EJ., Maarschalk-Ellerbroek, LJ., Oosterheert, JJ., Arends, JE., Wassenberg, MW., van der Hilst JC., Richter, C., van der Berg JP., Gisolf, EH., Margolick, JB., Plankey, M., Crain, B., Dobs, A., Farzadegan, H., Gallant, J., Johnson-Hill, L., Sacktor, N., Selnes, O., Shepard, J., Thio, C., Phair, JP., Wolinsky, SM., Badri, S., Conover, C., O'Gorman, M., Ostrow, D., Palella, F., Ragin, A., Detels, R., Martínez-Maza, O., Aronow, A., Bolan, R., Breen, E., Butch, A., Fahey, J., Jamieson, B., Miller, EN., Oishi, J., Vinters, H., Visscher, BR., Wiley, D., Witt, M., Yang, O., Young, S., Zhang, ZF., Rinaldo, CR., Becker, JT., Cranston, RD., Martinson, JJ., Mellors, JW., Silvestre, AJ., Stall, RD., Muñoz, A., Abraham, A., Althoff, K., Cox, C., D'Souza, G., Gange, SJ., Golub, E., Schollenberger, J., Seaberg, EC., Su, S., Huebner, RE., Dominguez, G., Moroni, M., Angarano, G., Antinori, A., Carosi, G., Cauda, R., Monforte£££A d'Arminio£££ A., Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Perno, CF., Sagnelli, E., Viale, PL., Von Schlosser, F., d'Arminio Monforte, A., Ammassari, A., Andreoni, M., Balotta, C., Bonfanti, P., Bonora, S., Borderi, M., Capobianchi, MR., Castagna, A., Ceccherini-Silberstein, F., Cozzi-Lepri, A., Gargiulo, M., Gervasoni, C., Girardi, E., Lichtner, M., Lo Caputo, S., Madeddu, G., Maggiolo, F., Marcotullio, S., Monno, L., Murri, R., Mussini, C., Puoti, M., Formenti, T., Galli, L., Lorenzini, P., Montroni, M., Giacometti, A., Costantini, A., Riva, A., Tirelli, U., Martellotta, F., Ladisa, N., Lazzari, G., Verucchi, G., Castelli, F., Scalzini, A., Minardi, C., Bertelli, D., Quirino, T., Abeli, C., Manconi, PE., Piano, P., Vecchiet, J., Falasca, K., Carnevale, G., Lorenzotti, S., Sighinolfi, L., Segala, D., Leoncini, F., Mazzotta, F., Pozzi, M., Cassola, G., Viscoli, G., Viscoli, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Caramma, I., Chiodera, A., Castelli, P., Rizzardini, G., Ridolfo, AL., Foschi, A., Salpietro, S., Galli, A., Bigoloni, A., Spagnuolo, V., Merli, S., Carenzi, L., Moioli, MC., Cicconi, P., Bisio, L., Gori, A., Lapadula, G., Abrescia, N., Chirianni, A., De Marco, M., Ferrari, C., Borghi, R., Baldelli, F., Belfiori, B., Parruti, G., Ursini, T., Magnani, G., Ursitti, MA., Narciso, P., Tozzi, V., Vullo, V., d'Avino, A., Zaccarelli, M., Gallo, L., Acinapura, R., Capozzi, M., Libertone, R., Trotta, MP., Tebano, G., Cattelan, AM., Mura, MS., Caramello, P., Orofino, GC., Sciandra, M., Raise, Ebo, F., Pellizzer, G., Manfrin, V., McManus, H., Wright, S., Moore, R., Edwards, S., Medische Microbiologie, RS: CAPHRI School for Public Health and Primary Care, AII - Amsterdam institute for Infection and Immunity, Experimental Immunology, Other departments, Graduate School, APH - Amsterdam Public Health, Global Health, Medical Microbiology and Infection Prevention, Paediatric Infectious Diseases / Rheumatology / Immunology, Other Research, Obstetrics and Gynaecology, Infectious diseases, General Internal Medicine, Center of Experimental and Molecular Medicine, University of Zurich, Tarr, Philip E, Rotger, M, Glass, T, Junier, T, Lundgren, J, Neaton, J, Poloni, E, Van 'T Wout, A, Lubomirov, R, Colombo, S, Martinez, R, Rauch, A, Günthard, H, Neuhaus, J, Wentworth, D, Van Manen, D, Gras, L, Schuitemaker, H, Albini, L, Torti, C, Jacobson, L, Li, X, Kingsley, L, Carli, F, Guaraldi, G, Ford, E, Sereti, I, Hadigan, C, Martinez, E, Arnedo, M, Egaña Gorroño, L, Gatell, J, Law, M, Bendall, C, Petoumenos, K, Rockstroh, J, Wasmuth, J, Kabamba, K, Delforge, M, De Wit, S, Berger, F, Mauss, S, De Paz Sierra, M, Losso, M, Belloso, W, Leyes, M, Campins, A, Mondi, A, De Luca, A, Bernardino, I, Barriuso Iglesias, M, Torrecilla Rodriguez, A, Gonzalez Garcia, J, Arribas, J, Fanti, I, Gel, S, Puig, J, Negredo, E, Gutierrez, M, Domingo, P, Fischer, J, Fätkenheuer, G, Alonso Villaverde, C, Macken, A, Woo, J, Mcginty, T, Mallon, P, Mangili, A, Skinner, S, Wanke, C, Reiss, P, Weber, R, Bucher, H, Fellay, J, Telenti, A, Tarr, P, Gori, A, Junier, Thomas, Poloni, Estella S., Rotger, Margalida, Glass, Tracy R., Junier, Thoma, Lundgren, Jen, Neaton, James D., Van 't Wout, Angã©lique B., Lubomirov, Rubin, Colombo, Sara, Martinez, Raquel, Rauch, Andri, Gã¼nthard, Huldrych F., Neuhaus, Jacqueline, Wentworth, Deborah, Van Manen, Danielle, Gras, Luuk A., Schuitemaker, Hanneke, Albini, Laura, Torti, Carlo, Jacobson, Lisa P., Li, Xiuhong, Kingsley, Lawrence A., Carli, Federica, Guaraldi, Giovanni, Ford, Emily S., Sereti, Irini, Hadigan, Colleen, Martinez, Esteban, Arnedo, Mireia, Egaã±a gorroã±o, Lander, Gatell, Jose M., Law, Matthew, Bendall, Courtney, Petoumenos, Kathy, Rockstroh, Jã¼rgen, Wasmuth, Jan christian, Kabamba, Kabeya, Delforge, Marc, De Wit, Stephane, Berger, Florian, Mauss, Stefan, De Paz Sierra, Mariana, Losso, Marcelo, Belloso, Waldo H., Leyes, Maria, Campins, Antoni, Mondi, Annalisa, De Luca, Andrea, Bernardino, Ignacio, Barriuso iglesias, Mã³nica, Torrecilla rodriguez, Ana, Gonzalez garcia, Juan, Arribas, Josã© R., Fanti, Iuri, Gel, Silvia, Puig, Jordi, Negredo, Eugenia, Gutierrez, Mar, Domingo, Pere, Fischer, Julia, Fã¤tkenheuer, Gerd, Alonso villaverde, Carlo, Macken, Alan, Woo, Jame, Mcginty, Tara, Mallon, Patrick, Mangili, Alexandra, Skinner, Sally, Wanke, Christine A., Reiss, Peter, Weber, Rainer, Bucher, Heiner C., Fellay, Jacque, Telenti, Amalio, Tarr, Philip E. Swiss Hiv Cohort, and Castagna, Antonella
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Male ,HIV Infections ,Genome-wide association study ,030204 cardiovascular system & hematology ,2726 Microbiology (medical) ,10234 Clinic for Infectious Diseases ,Coronary artery disease ,0302 clinical medicine ,ddc:590 ,Risk Factors ,Abacavir ,80 and over ,genetics ,030212 general & internal medicine ,Family history ,Articles and Commentaries ,Aged, 80 and over ,education.field_of_study ,medicine.diagnostic_test ,traditional risk factor ,Single Nucleotide ,Middle Aged ,3. Good health ,Infectious Diseases ,traditional risk factors ,Cohort ,Female ,HIV infection ,antiretroviral therapy ,coronary artery disease ,Human ,medicine.drug ,Adult ,Microbiology (medical) ,medicine.medical_specialty ,Adolescent ,Population ,Infectious Disease ,610 Medicine & health ,Polymorphism, Single Nucleotide ,Genetic Predisposition to Disease ,Aged ,Coronary Artery Disease ,Humans ,Polymorphism ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,education ,Genetic testing ,business.industry ,Risk Factor ,2725 Infectious Diseases ,Odds ratio ,medicine.disease ,Immunology ,genetic ,business - Abstract
BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.
- Published
- 2013
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