Infectious Disease Service, Infektiologie & Spitalhygiene, Kantonsspital Bruderholz, University of Basel, 4101 Bruderholz, Switzerland.
Pharmacogenomics. 2010 Apr;11(4):587-94. doi: 10.2217/pgs.10.35.
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.
HIV 感染者可能会加速动脉粥样硬化形成，并增加早发冠心病的风险。血脂异常是主要的动脉粥样硬化形成机制。在 HIV 感染者中，血脂异常通常归因于抗逆转录病毒治疗的不良反应。最近的 9 项全基因组关联研究提供了一个全面、无偏的常见单核苷酸多态性（SNP）清单，这些 SNP 可在一般人群中重复与血脂异常相关。全基因组关联研究验证的 SNP 现在已经证明在 HIV 感染和抗逆转录病毒治疗的情况下会导致血脂异常。在瑞士 HIV 感染者研究人群中，抗逆转录病毒治疗和遗传背景解释了类似比例的血清脂质变异性。在个体患者中，抗逆转录病毒治疗和 SNP 的累积效应都会增加患低高密度脂蛋白胆固醇、低高密度脂蛋白胆固醇血症和高甘油三酯血症的风险。遗传变异可能会导致 HIV 感染者出现其他主要代谢并发症，包括糖尿病和冠心病。为了解释复杂代谢特征遗传率的比例不断增加，正在进行的大规模基因重测序研究集中在罕见 SNP 和结构性遗传变异的影响上。
