Department of Epidemiology, University of Alabama at Birmingham, Alabama, USA.
Pharmacogenet Genomics. 2011 Dec;21(12):798-807. doi: 10.1097/FPC.0b013e32834b68f9.
Genetic studies may help explain abnormalities of fat distribution in HIV-infected patients treated with antiretroviral therapy (ARV).
Subcutaneous adipose tissue (SAT) volume measured by MRI in the leg, the lower trunk, the upper trunk, and the arm was examined in 192 HIV-infected White men, ARV-treated from the Fat Redistribution and Metabolic Change in HIV infection study. Single-nucleotide polymorphisms were assayed using the Illumina Human CNV370-quad beadchip. Multivariate and univariate genome-wide association analyses of the four SAT depots were implemented in PLINK software adjusted for age and ARV duration. Functional annotation analysis using Ingenuity Systems Pathway Analysis tool was carried out for markers with P lower than 10(-3) near known genes identified by multivariate analysis.
Loci (rs10504906, rs13267998, rs921231) in or near the anion exchanger solute carrier family 26, member 7 isoform a (SLC26A7) were strongly associated with the upper trunk and the arm SAT (9.8×10(-7) ≤P<7.8×10(-6)). Loci (rs193139, rs7523050, rs1761621) in and near a gene-rich region including G-protein-signaling modulator 2 (GPSM2) and syntaxin-binding protein 3 (STXBP3) were significantly associated with the lower body SAT depots (9.9×10(-7) ≤P<9.5×10(-6)). GPSM2 is associated with cell division and cancer whereas STXBP3 is associated with glucose metabolism in adipoctyes. Ingenuity Systems Pathway Analysis identified atherosclerosis, mitochondrial function, and T-cell-mediated apoptosis as processes related to SAT volume in HIV-infected individuals (P<5×10(-3)).
Our results are limited by the small sample size and replication is needed; however, this genomic scan uncovered new genes associated with metabolism and inflammatory pathways that may affect SAT volume in ARV-treated HIV-infected patients.
遗传研究可能有助于解释接受抗逆转录病毒治疗（ARV）的 HIV 感染者脂肪分布异常。
在 Fat Redistribution and Metabolic Change in HIV infection 研究中，对 192 名接受 ARV 治疗的白种 HIV 感染男性的腿部、下躯干、上躯干和手臂的皮下脂肪组织（SAT）体积进行了 MRI 测量。使用 Illumina Human CNV370-quad beadchip 检测单核苷酸多态性。使用 PLINK 软件对四个 SAT 库进行多变量和单变量全基因组关联分析，并针对年龄和 ARV 持续时间进行了调整。对多变量分析确定的已知基因附近的标记（P<10(-3)），使用 Ingenuity Systems Pathway Analysis 工具进行功能注释分析。
位于阴离子交换溶质载体家族 26 成员 7 异构体 a（SLC26A7）内或附近的位点（rs10504906、rs13267998、rs921231）与上躯干和手臂 SAT 强烈相关（9.8×10(-7)≤P<7.8×10(-6)）。位于富含基因区域（包括 G 蛋白信号调节因子 2（GPSM2）和突触结合蛋白 3（STXBP3））内或附近的位点（rs193139、rs7523050、rs1761621）与下躯干 SAT 库显著相关（9.9×10(-7)≤P<9.5×10(-6)）。GPSM2 与细胞分裂和癌症有关，而 STXBP3 与脂肪细胞中的葡萄糖代谢有关。Ingenuity Systems Pathway Analysis 确定了动脉粥样硬化、线粒体功能和 T 细胞介导的细胞凋亡是与 HIV 感染者 SAT 体积相关的过程（P<5×10(-3)）。
我们的结果受到样本量小的限制，需要进行复制；然而，这项基因组扫描揭示了与代谢和炎症途径相关的新基因，这些基因可能影响接受 ARV 治疗的 HIV 感染者的 SAT 体积。
