Journal
PHARMACOGENETICS AND GENOMICS
Volume 21, Issue 12, Pages 798-807Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0b013e32834b68f9
Keywords
GWAS; HAART; HIV; SAT; subcutaneous fat
Funding
- NIH [RO1-DK57508, HL74814, HL 53359, K23 AI66943, UL1 RR024131]
- NIH GCRC [M01-RR00036, RR00051, RR00052, RR00054, RR00083, RR0636, RR00865]
- Albert L. and Janet A. Schultz Supporting Foundation
- [K01 DK080188]
- [T32 NS054584]
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Objective Genetic studies may help explain abnormalities of fat distribution in HIV-infected patients treated with antiretroviral therapy (ARV). Methods 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. Results 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 x 10(-7) <= P < 7.8 x 10(-6)). Loci (rs193139, rs7523050, rs1761621) in and near a generich 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 x 10(-7) <= P<9.5 x 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 x 10(-3)). Conclusion 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. Pharmacogenetics and Genomics 21:798-807 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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