title: The g.-469G>A polymorphism in the GPIHBP1 gene promoter is associated with hypertriglyceridemia and has an additive effect on the risk conferred by LPL defective alleles.
abstract: OBJECTIVE
  Hypertriglyceridemia (hyperTG) is a component of the metabolic syndrome and a cardiovascular or pancreatitis risk factor. Although both genetic and environmental factors influence its expression, the biological component of hyperTG is still underestimated and has been reported in 10-20% of cases only. Given its key role in the lipolysis of TG-rich lipoproteins, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) is a biological candidate for hyperTG. The aim of this study was to assess the association of new GPIHBP1 gene variants with hyperTG (fasting plasma TG values ≥ 2.0 mmol/L).
  
  
  RESULTS
  Sequencing the GPIHBP1 gene identified a g.-469G > A (rs72691625) polymorphism in the promoter. A sample of 541 Caucasians (263 normoTG and 278 hyperTG) was then screened for this polymorphism using a 5'nuclease TaqMan. In multivariate analyses, GPIHBP1 g.-469G > A polymorphism carriers were at significantly higher risk of hyperTG (≥ 2.0 mmol/L) than non-carriers, the odds ratio (OR) being 1.67 (p = 0.025) among heterozygotes and 5.70 (p = 0.004) in homozygotes. The simultaneous presence of loss-of-function LPL polymorphisms had an incremental additive effect on the risk of hyperTG (OR: 7.30; p < 0.001), highlighting the importance of gene-gene interactions in the expression of hyperTG.
  
  
  CONCLUSIONS
  In this study, the g.-469G >A polymorphism in the GPIHBP1 gene promoter was associated with an increased risk of hyperTG and had an additive effect on the risk conferred by LPL defective alleles.
authors: Department of Medicine, Université de Montréal, ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, Saguenay, QC, Canada. simon-pierre.guay@ecogene21.org
authors: S P
authors: SP
authors: Guay
authors: D
authors: D
authors: Gaudet
authors: D
authors: D
authors: Brisson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011792:Quebec / Q000453:epidemiology; D018110:Receptors, Lipoprotein / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein; D014280:Triglycerides; C548261:LPL protein, human; D008071:Lipoprotein Lipase