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

Margalida Rotger, Tracy R. Glass, Thomas Junier, Jens Lundgren, James D. Neaton, Estella S. Poloni, Angélique B. Van 'T Wout, Rubin Lubomirov, Sara Colombo, Raquel Martinez, Andri Rauch, Huldrych F. Günthard, Jacqueline Neuhaus, Deborah Wentworth, Danielle Van Manen, Luuk A. Gras, Hanneke Schuitemaker, Laura Albini, Carlo Torti, Lisa P. JacobsonXiuhong Li, Lawrence A. Kingsley, Federica Carli, Giovanni Guaraldi, Emily S. Ford, Irini Sereti, Colleen Hadigan, Esteban Martinez, Mireia Arnedo, Lander Egaña-Gorroño, Jose M. Gatell, Matthew Law, Courtney Bendall, Kathy Petoumenos, Jürgen Rockstroh, Jan Christian Wasmuth, Kabeya Kabamba, Marc Delforge, Stephane De Wit, Florian Berger, Stefan Mauss, Mariana De Paz Sierra, Marcelo Losso, Waldo H. Belloso, Maria Leyes, Antoni Campins, Annalisa Mondi, Andrea De Luca, Ignacio Bernardino, Mónica Barriuso-Iglesias, Ana Torrecilla-Rodriguez, Juan Gonzalez-Garcia, José R. Arribas, Iuri Fanti, Silvia Gel, Jordi Puig, Eugenia Negredo, Mar Gutierrez, Pere Domingo, Julia Fischer, Gerd Fätkenheuer, Carlos Alonso-Villaverde, Alan MacKen, James Woo, Tara McGinty, Patrick Mallon, Alexandra Mangili, Sally Skinner, Christine A. Wanke, Peter Reiss, Rainer Weber, Heiner C. Bucher, Jacques Fellay, Amalio Telenti, Philip E. Tarr

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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. © 2013 The Author.
Original languageEnglish
Pages (from-to)112-121
JournalClinical Infectious Diseases
Volume57
Issue number1
DOIs
Publication statusPublished - 1 Jul 2013

Keywords

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

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