Department of Medicine, Université de Montréal, ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, Saguenay, QC, Canada.
Nutr Metab Cardiovasc Dis. 2013 Apr;23(4):358-65. doi: 10.1016/j.numecd.2011.08.005. Epub 2011 Oct 5.
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).
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.
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.
高甘油三酯血症（hyperTG）是代谢综合征的一个组成部分，也是心血管疾病或胰腺炎的一个风险因素。尽管遗传和环境因素都影响其表达，但高 TG 的生物学成分仍被低估，仅在 10-20%的病例中报告过。鉴于其在富含甘油三酯的脂蛋白的脂肪分解中起着关键作用，糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白 1（GPIHBP1）是高 TG 的一个生物学候选物。本研究旨在评估新的 GPIHBP1 基因突变与高甘油三酯血症（空腹血浆甘油三酯值≥2.0mmol/L）之间的关联。
对 GPIHBP1 基因进行测序，在启动子中发现了一个 g.-469G > A（rs72691625）多态性。然后，对 541 名高加索人（263 名正常 TG 组和 278 名高 TG 组）样本进行了该多态性的筛查，使用 5'nuclease TaqMan。在多变量分析中，GPIHBP1 g.-469G > A 多态性携带者患高甘油三酯血症（≥2.0mmol/L）的风险明显高于非携带者，杂合子的比值比（OR）为 1.67（p=0.025），纯合子的 OR 为 5.70（p=0.004）。同时存在失活 LPL 多态性对高甘油三酯血症的风险有累加附加效应（OR：7.30；p < 0.001），突出了基因-基因相互作用在高甘油三酯血症表达中的重要性。
在本研究中，GPIHBP1 基因启动子中的 g.-469G > A 多态性与高甘油三酯血症风险增加相关，并对 LPL 缺陷等位基因赋予的风险具有累加效应。
