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Clin Infect Dis. 2013 Jul;57(1):112-21. doi: 10.1093/cid/cit196. Epub 2013 Mar 26.

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

Collaborators (439)

Rotger M, Glass TR, Lubomirov R, Bucher HC, Telenti A, Tarr PE, Junier T, Poloni ES, Fellay J, Glass TR, Colombo S, Lubomirov R, Martinez R, Rotger M, Rauch A, Weber R, Günthard HF, Bucher HC, Fellay J, Telenti A, Tarr PE, 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 M, Rodriguez AT, Garcia JG, Arribas JR, Fanti I, De Luca A, 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, Bucher HC, Burton-Jeangros C, Calmy A, Cavassini M, Egger M, Elzi L, Fehr J, Fellay 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, Rauch A, Regenass S, Rickenbach M, Rudin C, Schmid P, Schultze D, Schöni-Affolter F, Schüpbach J, Speck R, Taffé P, Tarr P, Telenti A, Trkola A, Vernazza P, Weber R, Prins YS, Kuijpers TW, Scherpbier HJ, Boer K, van der Meer JT, Wit FW, Godfried MH, Reiss P, 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, Kingsley LA, Becker JT, Cranston RD, Martinson JJ, Mellors JW, Silvestre AJ, Stall RD, Jacobson LP, 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, 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, Antinori A, Balotta C, Bonfanti P, Bonora S, Borderi M, Capobianchi MR, Castagna A, Ceccherini-Silberstein F, Cozzi-Lepri A, Monforte A, De Luca 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, Torti C, Cozzi-Lepri A, Fanti I, Formenti T, Galli L, Lorenzini P, Montroni M, Giacometti A, Costantini A, Riva A, Tirelli U, Martellotta F, Angarano G, Monno L, Ladisa N, Maggiolo F, Lazzari G, Viale PL, Borderi M, Verucchi G, Castelli F, Scalzini A, Torti C, 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, Lo Caputo S, Cassola G, Viscoli G, Viscoli A, Piscopo R, Mazzarello G, Mastroianni C, Belvisi V, Bonfanti P, Caramma I, Chiodera A, Castelli P, Galli M, Lazzarin A, Rizzardini G, Puoti M, Monforte A, Ridolfo AL, Foschi A, Castagna A, Salpietro S, Galli A, Bigoloni A, Spagnuolo V, Merli S, Carenzi L, Moioli MC, Cicconi P, Formenti T, Mussini C, Bisio L, Gori A, Lapadula G, Abrescia N, Chirianni A, De Marco M, Gargiulo M, Ferrari C, Borghi R, Baldelli F, Belfiori B, Parruti G, Ursini T, Magnani G, Ursitti MA, Cauda R, Andreoni M, Antinori A, Narciso P, Tozzi V, Vullo V, De Luca A, d'Avino A, Zaccarelli M, Gallo L, Acinapura R, Capozzi M, Libertone R, Trotta MP, Lichtner M, Tebano G, Cattelan AM, Mura MS, Madeddu G, Caramello P, Di Perri G, Orofino GC, Sciandra M, Raise, Ebo F, Pellizzer G, Manfrin V, Law M, Petoumenos K, McManus H, Wright S, Bendall C, Moore R, Edwards S.

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.

KEYWORDS:

HIV infection; antiretroviral therapy; coronary artery disease; genetics; traditional risk factors

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