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载脂蛋白 LPL 基因多态性与 LDL、HDL、VLDL 胆固醇和甘油三酯水平与缺血性卒中及其亚型的关系。

Association of LPL gene variant and LDL, HDL, VLDL cholesterol and triglyceride levels with ischemic stroke and its subtypes.

机构信息

Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad-500016, India.

出版信息

J Neurol Sci. 2012 Jul 15;318(1-2):51-4. doi: 10.1016/j.jns.2012.04.006. Epub 2012 Apr 26.

DOI:10.1016/j.jns.2012.04.006
PMID:22541364
Abstract

Lipoprotein lipase (LPL) plays an important role in lipid metabolism by hydrolyzing triglycerides in chylomicrons and very low density lipoproteins. An increasing number of studies have suggested an association of LPL gene variants with the risk of cardiovascular and cerebrovascular diseases. The aim of this study was to test whether HindIII polymorphism of LPL gene is associated with ischemic stroke and its subtypes as well as plasma lipid levels in a South Indian population from Andhra Pradesh. Five hundred and twenty five ischemic stroke patients and 500 controls were enrolled in this case-control study. The LPL HindIII polymorphism was determined by PCR-RFLP technique and the lipid levels were estimated using commercially available kits. We found significant difference in the genotypic distribution between patients and controls [for HindIII (+/+) vs. HindIII (-/-), χ(2)=4.916; p=0.02; Odds ratio=1.59 (95%CI; 1.054-2.413); HindIII (+/+) vs. HindIII (-/-) and HindIII (+/-), χ(2)=5.25; p=0.02; Odds ratio=1.24 (95%CI; 1.03-1.503)]. A stepwise multiple logistic regression analysis confirmedthese findings. The relationship between HindIII genotypes and plasma levels of HDL, LDL, VLDL and triglycerides was analyzed using ANOVA and further confirmed by Post-hoc analysis. The levels of triglycerides were found to be elevated in individuals bearing HindIII (+/+) genotype in comparison with HindIII (-/-) genotype. HDL levels were found to be significantly reduced and triglyceride levels significantly elevated in HindIII (+/+) genotype in comparison with HindIII (-/-). However, there was no difference in the levels of LDL and VLDL between the two genotypes. Examining the association of LPL gene HindIII polymorphism with stroke subtypes, we found significant association of HindIII polymorphism with Intracranial large artery atherosclerosis [Odds ratio=2.12 955CI (1.656-2.848); p=0.009]. Our results suggest that the HindIII polymorphism of LPL is significantly associated with ischemic stroke risk and elevated levels of plasma triglycerides and reduced HDL levels. Further, this polymorphism is significantly associated with intracranial large artery atherosclerosis which is the most frequent subtype in our region.

摘要

脂蛋白脂肪酶(LPL)通过水解乳糜微粒和极低密度脂蛋白中的甘油三酯,在脂质代谢中发挥重要作用。越来越多的研究表明,LPL 基因变异与心血管和脑血管疾病的风险相关。本研究旨在检验印度安得拉邦南部人群中 LPL 基因 HindIII 多态性与缺血性脑卒中及其亚型以及血浆脂质水平的相关性。本病例对照研究纳入了 525 例缺血性脑卒中患者和 500 例对照。采用 PCR-RFLP 技术检测 LPL HindIII 多态性,采用商业试剂盒检测血脂水平。我们发现患者和对照组之间的基因型分布存在显著差异[对于 HindIII(+/+)与 HindIII(-/-),χ(2)=4.916;p=0.02;比值比=1.59(95%置信区间;1.054-2.413);HindIII(+/+)与 HindIII(-/-)和 HindIII(+/+),χ(2)=5.25;p=0.02;比值比=1.24(95%置信区间;1.03-1.503)]。逐步多因素逻辑回归分析证实了这些发现。采用方差分析(ANOVA)分析 HindIII 基因型与高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、极低密度脂蛋白(VLDL)和甘油三酯血浆水平的关系,并通过事后分析进一步证实。与 HindIII(-/-)基因型相比,HindIII(+/+)基因型个体的甘油三酯水平升高。与 HindIII(-/-)相比,HindIII(+/+)基因型的 HDL 水平显著降低,甘油三酯水平显著升高。然而,两种基因型之间的 LDL 和 VLDL 水平没有差异。研究 LPL 基因 HindIII 多态性与脑卒中亚型的相关性时,我们发现 HindIII 多态性与颅内大动脉粥样硬化显著相关[比值比=2.12,95%置信区间(1.656-2.848);p=0.009]。我们的结果表明,LPL 的 HindIII 多态性与缺血性脑卒中风险以及血浆甘油三酯水平升高和 HDL 水平降低显著相关。此外,这种多态性与颅内大动脉粥样硬化显著相关,这是我们地区最常见的亚型。

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