title: Association of GWAS-based candidate genes with HDL-cholesterol levels before and after bariatric surgery in the Swedish obese subjects study.
abstract: 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% at baseline and yr 2, respectively. LIPC SNP rs1077834 showed consistent associations 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.
authors.affiliation: Human Genomics Laboratory, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, Louisiana 70808-4124, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sarzynski
authors.forename: Peter
authors.initials: P
authors.lastname: Jacobson
authors.forename: Tuomo
authors.initials: T
authors.lastname: Rankinen
authors.forename: Björn
authors.initials: B
authors.lastname: Carlsson
authors.forename: Lars
authors.initials: L
authors.lastname: Sjöström
authors.forename: Lena M S
authors.initials: LM
authors.lastname: Carlsson
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
mesh_terms: D000483:Alleles; D050110:Bariatric Surgery; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; C504173:LIPC protein, human; D008049:Lipase; C548261:LPL protein, human; D008071:Lipoprotein Lipase