Dyslipidemia in HIV-infected individuals: from pharmacogenetics to pharmacogenomics.
HIV-infected individuals may have accelerated atherogenesis and an increased risk for premature coronary artery disease. Dyslipidemia represents a key pro-atherogenic mechanism. In HIV-infected patients, dyslipidemia is typically attributed to the adverse effects of antiretroviral therapy. Nine recent genome-wide association studies have afforded a comprehensive, unbiased inventory of common SNPs at 36 genetic loci that are reproducibly associated with dyslipidemia in the general population. Genome-wide association study-validated SNPs have now been demonstrated to contribute to dyslipidemia in the setting of HIV infection and antiretroviral therapy. In a Swiss HIV-infected study population, a similar proportion of serum lipid variability was explained by antiretroviral therapy and by genetic background. In the individual patient, both antiretroviral therapy and the cumulative effect of SNPs contribute to the risk of high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol and hypertriglyceridemia. Genetic variants presumably contribute to additional major metabolic complications in HIV-infected individuals, including diabetes mellitus and coronary artery disease. In an effort to explain an increasing proportion of the heritability of complex metabolic traits, ongoing large-scale gene resequencing studies are focusing on the effects of rare SNPs and structural genetic variants.
Tarr
Philip E
PE
Infectious Disease Service, Infektiologie & Spitalhygiene, Kantonsspital Bruderholz, University of Basel, 4101 Bruderholz, Switzerland. philip.tarr@unibas.ch
Rotger
Margalida
M
Telenti
Amalio
A
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics; D003920:Diabetes Mellitus / Q000209:etiology / Q000235:genetics; D050171:Dyslipidemias / Q000097:blood / Q000139:chemically induced / Q000209:etiology / Q000235:genetics*; D015894:Genome, Human; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008055:Lipids / Q000097:blood; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
D019380:Anti-HIV Agents; D008055:Lipids