Rotger Margalida, Bayard Cornelia, Taffé Patrick, Martinez Raquel, Cavassini Matthias, Bernasconi Enos, Battegay Manuel, Hirschel Bernard, Furrer Hansjakob, Witteck Andrea, Weber Rainer, Ledergerber Bruno, Telenti Amalio, Tarr Philip E
Institute of Microbiology, University Hospital and University of Lausanne, Lausanne, Switzerland.
Circ Cardiovasc Genet. 2009 Dec;2(6):621-8. doi: 10.1161/CIRCGENETICS.109.874412. Epub 2009 Sep 18.
HIV-infected individuals have an increased risk of myocardial infarction. Antiretroviral therapy (ART) is regarded as a major determinant of dyslipidemia in HIV-infected individuals. Previous genetic studies have been limited by the validity of the single-nucleotide polymorphisms (SNPs) interrogated and by cross-sectional design. Recent genome-wide association studies have reliably associated common SNPs to dyslipidemia in the general population.
We validated the contribution of 42 SNPs (33 identified in genome-wide association studies and 9 previously reported SNPs not included in genome-wide association study chips) and of longitudinally measured key nongenetic variables (ART, underlying conditions, sex, age, ethnicity, and HIV disease parameters) to dyslipidemia in 745 HIV-infected study participants (n=34 565 lipid measurements; median follow-up, 7.6 years). The relative impact of SNPs and ART to lipid variation in the study population and their cumulative influence on sustained dyslipidemia at the level of the individual were calculated. SNPs were associated with lipid changes consistent with genome-wide association study estimates. SNPs explained up to 7.6% (non-high-density lipoprotein cholesterol), 6.2% (high-density lipoprotein cholesterol), and 6.8% (triglycerides) of lipid variation; ART explained 3.9% (non-high-density lipoprotein cholesterol), 1.5% (high-density lipoprotein cholesterol), and 6.2% (triglycerides). An individual with the most dyslipidemic antiretroviral and genetic background had an approximately 3- to 5-fold increased risk of sustained dyslipidemia compared with an individual with the least dyslipidemic therapy and genetic background.
In the HIV-infected population treated with ART, the weight of the contribution of common SNPs and ART to dyslipidemia was similar. When selecting an ART regimen, genetic information should be considered in addition to the dyslipidemic effects of ART agents.
HIV感染者发生心肌梗死的风险增加。抗逆转录病毒疗法（ART）被认为是HIV感染者血脂异常的主要决定因素。以往的基因研究受到所检测单核苷酸多态性（SNP）的有效性以及横断面设计的限制。近期的全基因组关联研究已可靠地将常见SNP与普通人群的血脂异常关联起来。
我们在745名HIV感染的研究参与者中（n = 34565次血脂测量；中位随访时间为7.6年），验证了42个SNP（33个在全基因组关联研究中鉴定出，9个先前报道的未包含在全基因组关联研究芯片中的SNP）以及纵向测量的关键非遗传变量（ART、基础疾病、性别、年龄、种族和HIV疾病参数）对血脂异常的影响。计算了SNP和ART对研究人群血脂变化的相对影响及其对个体持续性血脂异常的累积影响。SNP与血脂变化的关联与全基因组关联研究估计结果一致。SNP分别解释了高达7.6%（非高密度脂蛋白胆固醇）、6.2%（高密度脂蛋白胆固醇）和6.8%（甘油三酯）的血脂变化；ART分别解释了3.9%（非高密度脂蛋白胆固醇）、1.5%（高密度脂蛋白胆固醇）和6.2%（甘油三酯）的血脂变化。与抗逆转录病毒和遗传背景导致血脂异常最少的个体相比，抗逆转录病毒和遗传背景导致血脂异常最严重的个体发生持续性血脂异常的风险增加约3至5倍。
在接受ART治疗的HIV感染人群中，常见SNP和ART对血脂异常的贡献程度相似。在选择ART方案时，除了考虑ART药物的血脂异常影响外，还应考虑遗传信息。
