Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons
Por:
Rotger, M, Glass, TR, Junier, T, Lundgren, J, Neaton, JD, Poloni, ES, van 't Wout, AB, Lubomirov, R, Colombo, S, Martinez, R, Rauch, A, Gunthard, HF, Neuhaus, J, Wentworth, D, van Manen, D, Gras, LA, Schuitemaker, H, Albini, L, Torti, C, Jacobson, LP, Li, XH, Kingsley, LA, Carli, F, Guaraldi, G, Ford, ES, Sereti, I, Hadigan, C, Martinez, E, Arnedo, M, Egana-Gorrono, 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, MD, 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, Fatkenheuer, 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
Publicada:
1 jul 2013
Resumen:
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 = 2.9x10(-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.
Filiaciones:
Rotger, M:
Univ Lausanne, Univ Hosp Ctr, Inst Microbiol, CH-1015 Lausanne, Switzerland
Glass, TR:
Univ Basel Hosp, Basel Inst Clin Epidemiol & Biostat, Basel, Switzerland
Junier, T:
Swiss Inst Bioinformat, Lausanne, Switzerland
Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland
Lundgren, J:
Univ Copenhagen, DK-1168 Copenhagen, Denmark
Neaton, JD:
Univ Minnesota, Minneapolis, MN USA
Poloni, ES:
Univ Geneva, Dept Genet & Evolut, Lab Anthropol, Bern, Switzerland
van 't Wout, AB:
AIDS Therapy Evaluat Netherlands, Amsterdam, Netherlands
Lubomirov, R:
Univ Lausanne, Univ Hosp Ctr, Inst Microbiol, CH-1015 Lausanne, Switzerland
Colombo, S:
Univ Lausanne, Univ Hosp Ctr, Inst Microbiol, CH-1015 Lausanne, Switzerland
Martinez, R:
Univ Lausanne, Univ Hosp Ctr, Inst Microbiol, CH-1015 Lausanne, Switzerland
Rauch, A:
Swiss HIV Cohort Study, Bern, Switzerland
Univ Hosp Bern, Div Infect Dis, CH-3010 Bern, Switzerland
Gunthard, HF:
Swiss HIV Cohort Study, Bern, Switzerland
Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Bern, Switzerland
Neuhaus, J:
Univ Minnesota, Minneapolis, MN USA
Wentworth, D:
Univ Minnesota, Minneapolis, MN USA
van Manen, D:
AIDS Therapy Evaluat Netherlands, Amsterdam, Netherlands
Gras, LA:
AIDS Therapy Evaluat Netherlands, Amsterdam, Netherlands
Schuitemaker, H:
AIDS Therapy Evaluat Netherlands, Amsterdam, Netherlands
Albini, L:
Univ Brescia, Dept Infect Dis, Catanzaro, Italy
Torti, C:
Univ Brescia, Dept Infect Dis, Catanzaro, Italy
Magna Graecia Univ Catanzaro, Infect Dis Unit, Catanzaro, Italy
Carli, F:
Univ Modena & Reggio Emilia, Modena, Italy
Guaraldi, G:
Univ Modena & Reggio Emilia, Modena, Italy
Ford, ES:
Intramural Natl Inst Allergy & Infect Dis Cohort, Bethesda, MD USA
Sereti, I:
Intramural Natl Inst Allergy & Infect Dis Cohort, Bethesda, MD USA
Hadigan, C:
Intramural Natl Inst Allergy & Infect Dis Cohort, Bethesda, MD USA
Martinez, E:
Hosp Clin IDIBAPS, Barcelona, Spain
Arnedo, M:
Hosp Clin IDIBAPS, Barcelona, Spain
Egana-Gorrono, L:
Hosp Clin IDIBAPS, Barcelona, Spain
Gatell, JM:
Hosp Clin IDIBAPS, Barcelona, Spain
Law, M:
Univ New S Wales, Kirby Inst, Australian HIV Observat Database, Darlinghurst, NSW, Australia
Bendall, C:
Univ New S Wales, Kirby Inst, Australian HIV Observat Database, Darlinghurst, NSW, Australia
Petoumenos, K:
Univ New S Wales, Kirby Inst, Australian HIV Observat Database, Darlinghurst, NSW, Australia
Rockstroh, J:
Univ Hosp Bonn, Bonn, Germany
Wasmuth, JC:
Univ Hosp Bonn, Bonn, Germany
Kabamba, K:
St Pierre Univ Hosp, Brussels, Belgium
Delforge, M:
St Pierre Univ Hosp, Brussels, Belgium
De Wit, S:
St Pierre Univ Hosp, Brussels, Belgium
Berger, F:
Ctr HIV Hepatogastroenterol Dusseldorf, Dusseldorf, Germany
Mauss, S:
Ctr HIV Hepatogastroenterol Dusseldorf, Dusseldorf, Germany
Sierra, MD:
Cohorte LATINA Argentinian Component, Buenos Aires, DF, Argentina
Losso, M:
Cohorte LATINA Argentinian Component, Buenos Aires, DF, Argentina
Belloso, WH:
Cohorte LATINA Argentinian Component, Buenos Aires, DF, Argentina
Leyes, M:
Univ Hosp Son Espases, Palma De Mallorca, Spain
Campins, A:
Univ Hosp Son Espases, Palma De Mallorca, Spain
Mondi, A:
Univ Cattolica Sacro Cuore, Rome, Italy
De Luca, A:
Univ Cattolica Sacro Cuore, Rome, Italy
Bernardino, I:
Univ Hosp La Paz, Madrid, Spain
IdiPAZ Biobanco, Madrid, Spain
Barriuso-Iglesias, M:
Univ Hosp La Paz, Madrid, Spain
IdiPAZ Biobanco, Madrid, Spain
Torrecilla-Rodriguez, A:
Univ Hosp La Paz, Madrid, Spain
IdiPAZ Biobanco, Madrid, Spain
Gonzalez-Garcia, J:
Univ Hosp La Paz, Madrid, Spain
IdiPAZ Biobanco, Madrid, Spain
Arribas, JR:
Univ Hosp La Paz, Madrid, Spain
IdiPAZ Biobanco, Madrid, Spain
Gel, S:
Univ Hosp Germans Trias & Pujol, Badalona, Spain
Puig, J:
Univ Hosp Germans Trias & Pujol, Badalona, Spain
Negredo, E:
Univ Hosp Germans Trias & Pujol, Badalona, Spain
Gutierrez, M:
Autonomous Univ Barcelona, Univ Hosp Santa Creu & St Pau Cohort, Barcelona, Spain
Domingo, P:
Autonomous Univ Barcelona, Univ Hosp Santa Creu & St Pau Cohort, Barcelona, Spain
Fischer, J:
Univ Hosp Cologne, Cologne, Germany
Fatkenheuer, G:
Univ Hosp Cologne, Cologne, Germany
Alonso-Villaverde, C:
Hosp Santa Tecla & St Pau, Tarragona, Spain
Macken, A:
Univ Coll Dublin, Sch Med & Med Sci, Dublin, Ireland
Woo, J:
St James Hosp, Dublin, Ireland
McGinty, T:
Mater Misericordiae Univ Hosp, Dublin, Ireland
Mallon, P:
Univ Coll Dublin, Sch Med & Med Sci, Dublin, Ireland
Mangili, A:
Tufts Univ, Sch Med, Boston, MA 02111 USA
Skinner, S:
Tufts Univ, Sch Med, Boston, MA 02111 USA
Wanke, CA:
Tufts Univ, Sch Med, Boston, MA 02111 USA
Reiss, P:
AIDS Therapy Evaluat Netherlands, Amsterdam, Netherlands
Weber, R:
Swiss HIV Cohort Study, Bern, Switzerland
Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Bern, Switzerland
Bucher, HC:
Univ Basel Hosp, Basel Inst Clin Epidemiol & Biostat, Basel, Switzerland
Swiss HIV Cohort Study, Bern, Switzerland
Fellay, J:
Univ Lausanne, Univ Hosp Ctr, Inst Microbiol, CH-1015 Lausanne, Switzerland
Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland
Swiss HIV Cohort Study, Bern, Switzerland
Telenti, A:
Univ Lausanne, Univ Hosp Ctr, Inst Microbiol, CH-1015 Lausanne, Switzerland
Swiss HIV Cohort Study, Bern, Switzerland
Tarr, PE:
Swiss HIV Cohort Study, Bern, Switzerland
Univ Basel, Kantonsspital Baselland, Bruderholz, Bern, Switzerland
Green Published, Bronze, Green Accepted
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