遗传相关的低高密度脂蛋白胆固醇血症与冠状动脉性心脏病的关系:荟萃分析  

Relationship between genetically-related low plasma high-density lipoprotein cholesterol and coronary heart disease:a meta-analysis

作　　者：卢卓强[1] 晋学庆[2] 龚晶婧[1] 蔡瀚[1] 林金秀[1] 

机构地区：[1]福建医科大学附属第一医院心内科福建省高血压研究所,福建福州350005 [2]福建医科大学附属第一医院内四科,福建福州350005

出　　处：《中华高血压杂志》2016年第11期1059-1069,共11页Chinese Journal of Hypertension

摘　　要：目的 以胆固醇酯转运蛋白（CETP）基因-629位点C/A变异为工具变量,通过孟德尔随机化荟萃分析探讨血浆高密度脂蛋白胆固醇（HDL-C）与冠状动脉性心脏病（冠心病）发病风险之间的潜在因果关系。方法检索PubMed和EMBASE数据库,收集2015年12月以前发表的关于CETP-629C/A多态性与冠心病及血脂水平相关性的所有前瞻性或回顾性研究,利用STATA软件对HDL-C与冠心病的相关性进行荟萃分析。结果 总共有12篇（包括15组研究群体：冠心病患者4894例,对照人群7462名）关于CETP-629C/A多态性与冠心病发病风险的巢式病例对照研究和9篇（包括19组研究群体,22 140名研究对象）关于CETP-629C/A多态性与血浆三酰甘油和（或）HDL-C水平相关性的文献纳入分析。总体分析表明,CETP-629C等位基因在等位基因模型、纯合子模型和显性模型下分别使患冠心病的风险增加3%（OR=1.03,95%CI 0.93~1.14,P=0.603）,12%（OR=1.12,95%CI0.95~1.32,P=0.186）和11%（OR=1.11,95%CI0.96~1.28,P=0.174）,但结果无统计学意义。亚组分析显示,在关于高加索人、心肌梗死患者、前瞻性或大规模的研究中,携带-629C等位基因增加罹患冠心病的风险（P〈0.05）。-629CC基因型人群[加权均数差（WMD）-3.48,P〈0.01]或携带-629C等位基因人群（WMD-3.01,P〈0.01）血浆中的HDL-C水平均显著降低。而不同基因型人群的血浆三酰甘油水平差别没有统计学意义;孟德尔随机化分析中,由遗传因素所致血浆中HDL-C水平下降1、5、10mg/dL（1mg/dL=0.026mmol/L）的因果关系优势比在高加索人中分别为1.11、1.67、2.79,心肌梗死患者中分别为1.07、1.43、2.03,前瞻性研究中分别为1.07、1.41、1.99,大规模研究中分别为1.07、1.38、1.90。结论 遗传相关的低HDL-C血症在高加索人群中作为冠心病的危险因素有临床意义。Objective To examine the potential causal relevance of high-density lipoprotein cholesterol （HDL-C） for coronary heart disease （CHD） using cholesteryl ester transfer p rotein（CETP） gene -629C/A variant as an instru- ment in a Mendelian randomization meta-analysis. Methods Eligible prospective or retrospective studies about the CETP -629C/A variant association with CHD and lipid profile were identified by searching PubMed and EMBASE till December 2015. Data were assessed in duplicate and analyzed by STATA software. Results A total of 12 nested case-control studies were eligible for the genotype-disease association and 9 for the genotype-phenotype associ- ation. Overall analyses indicated that the -629C allele was nonsignificantly associated with 3 % （OR= 1.03, 95 % CI 0.93-I. 14, P=0.603）, 12% （OR=1.12, 95% CI 0.95-1.32, P=0.186） and 11% （OR=1. 11, 95% CI 0.96=1. 28, P=0. 174） increased risk of CHD under the allelic, homozygous genotypic and dominant models, re- spectively. In subgroup analyses, the corresponding effect estimates were significant in Caucasians, for myocardial infarction, in prospective and large studies. Plasma HDL-C was significantly reduced in carriers of -629CC geno- type （weighted mean difference or WMD -3.48; P〈0.01） or -629C allele （WMD -3.01, P〈0.01）. No sig- nificant changes were identified for plasma triglyeerides. In the Mendelian randomization analysis, the significant causal odds ratio for a 1, 5, 10 mg/dL（l mg/dL=0. 026 mmol/L） genetic decrease of plasma HDL-C was 1. 11, 1. 67, 2.79 in Caucasians, 1.07, 1. 43, 2.03 for myocardial infarction, 1. 07, 1.41, 1.99 in prospective studies,1.07, 1.38, 1.90 in large studies, respectively. Conclusion This meta-analysis collectively reinforces the concept that genetically decreased plasma HDL-C is likely to be a potential causal risk factor for CHD, and this effect is more evident in Caucasians and for myocardial infarction.

关 键 词：冠状动脉性心脏病 三酰甘油 高密度脂蛋白胆固醇 胆固醇酯转运蛋白 孟德尔随机化 

分 类 号：R541.4[医药卫生—心血管疾病]