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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 investigate the relationship between plasma high density lipoprotein cholesterol (HDL-C) and coronary heart disease (CHD) by means of a Mendelian randomized meta-analysis using the C / A mutation at -629 site of cholesterol ester transporter (CETP) Potential causal relationship between risk of onset. Methods The PubMed and EMBASE databases were searched and all prospective or retrospective studies published in December 2015 on the association between CETP-629C / A polymorphisms and coronary heart disease and blood lipid levels were collected. Heart disease related meta-analysis. RESULTS: A total of 12 (including 15 study groups: 4894 CHD patients and 7462 control subjects) nested case-control studies on CETP-629C / A polymorphism and risk of CHD and 9 (including 19 Study population, and 22 140 subjects) were included in the literature on the association of CETP-629C / A polymorphism with plasma triglycerides and / or HDL-C levels. Overall analysis showed that the CETP-629C allele increased the risk of coronary heart disease by 3% (OR = 1.03, 95% CI 0.93 to 1.14, P = 0.603, respectively) in the allelic, homozygous and dominance models , 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), but the results were not statistically significant. Subgroup analyzes showed that carrying the -629C allele increased the risk of coronary heart disease (P <0.05) in prospective or large-scale studies in Caucasians and patients with myocardial infarction. The level of HDL-C in the plasma of -629CC genotype [WMD-3.48, P <0.01] or -629C allele (WMD-3.01, P <0.01) However, there was no significant difference in plasma triglyceride levels among different genotypes. In Mendel’s randomized study, plasma levels of HDL-C were decreased by genetic factors (1,5,10 mg / dL, 1 mg / dL = 0.026 mmol / / L) were 1.11, 1.67, 2.79 respectively in Caucasians, 1.07, 1.43, 2.03 in patients with myocardial infarction, 1.07, 1.41, 1.99 respectively in prospective studies, and in large studies were 1.07, 1.38, 1.90. Conclusions The genetic association of low HDL-C is clinically significant as a risk factor for coronary heart disease in the Caucasians.