Association of GWAS-based candidate genes with HDL-cholesterol levels before and after bariatric surgery in the Swedish Obese Subjects study

Abstract

Context and Objective: The magnitude of weight loss-induced high-density lipoprotein cholesterol (HDL-C) changes may depend on genetic factors. We examined the associations of eight candidate genes, identified by genome-wide association studies, with HDL-C at baseline and 10 yr after bariatric surgery in the Swedish Obese Subjects study. Methods: Single-nucleotide polymorphisms (SNP) (n = 60) in the following gene loci were genotyped: ABCA1, APOA5, CETP, GALNT2, LIPC, LIPG, LPL, and MMAB/MVK. Cross-sectional associations were tested before (n=1771) and 2 yr (n=1583) and 10 yr (n=1196) after surgery. Changes in HDL-C were tested between baseline and yr 2 (n = 1518) and yr 2 and 10 (n = 1149). A multiple testing corrected threshold of P = 0.00125 was used for statistical significance. Results: In adjusted multivariate models, CETP SNP rs3764261 explained from 3.2-4.2% (P<10-14) of the variation in HDL-C at all three time points, whereas CETP SNP rs9939224 contributed an additional 0.6 and 0.9% atbaselineandyr 2, respectively. LIPCSNPrs1077834showedconsistentassociations across all time points (R 2 = 0.4-1.1%; 3.8 × 10-6 < P < 3 × 10-3), whereas LPL SNP rs6993414 contributed approximately 0.5% (5 × 10-4 < P < 0.0012) at yr 2 and 10. In aggregate, four SNP in three genes explained 4.2, 6.8, and 5.6% of the HDL-C variance at baseline, yr 2, and yr 10, respectively. None of the SNP was significantly associated with weight loss-related changes in HDL-C. Conclusions: SNP in the CETP, LIPC, and LPL loci contribute significantly to plasma HDL-C levels in obese individuals, and the associations persist even after considerable weight loss due to bariatric surgery. However, they are not associated with surgery-induced changes in HDL-C levels. Copyright © 2011 by The Endocrine Society.