Background and aims: 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).
Methods and 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.
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