血管内皮生长因子基因多态性与先天性心脏病相关性的Meta分析

目的 评价血管内皮生长因子（VEGF）等位基因、基因型、基因单倍型多态性与先天性心脏病（CHD）的相关性.方法 检索Cochrane图书馆、Medline、PubMed、EMBASE、中国期刊全文数据库、万方数据库及中国生物医学文献数据库,检索起止时间均为建库至2011年12月,并且对重要文献的参考文献采取手工回溯检索.获取VEGF与CHD相关性的病例对照研究和传递不平衡检验文献.对文献进行质量评价.采用RevMan 5.1.1软件进行异质性检验,根据检验结果选择适当的效应模型进行Meta分析.结果 6篇文献共10项独立研究纳入分析,漏斗图检验存在发表偏倚.Meta分析结果显示：① VEGF C-2578A和G-1154A位点等位基因变异显著增加DiGeorge综合征患者的CHD易感性,OR分别为1.40（95%CI：1.04～1.16）和1.87（95%CI：1.27～2.75）;G-634C位点的等位基因变异显著增加普通病例的CHD易感性,OR=1.29,95%CI：1.02～1.62.② G-1154A位点（AA＋AG）为DiGeorge综合征患者合并CHD的危险因素,OR=2.10,95%CI：1.32～3.34.③单倍型AAG在DiGeorge综合征患者中显著增加CHD易感性,OR=1.82,95%CI：1.31～2.54;单倍型CGC显著降低普通病例CHD风险的保护作用,OR=0.79,95%CI：0.63～0.99.结论 VEGF等位基因、基因型、基因单倍型多态性与CHD易感性存在一定的相关性,且在DiGeorge综合征患者与普通患者间存在差异;在不伴DiGeorge综合征的人群中,特定单倍型（CGC）则有显著降低CHD风险的保护作用,其作用机制尚需进一步明确.

A meta-analysis of the association between vascular endothelial growth factor gene polymorphisms and congenital heart disease

Objective To evaluate the association between allele, genotypes and haplotype of vascular endothelial growth factor （VEGF） polymorphisms and congenital heart disease （CHD）. Methods Cochrane library, PubMed, EMBASE, Chinese National Knowledge Infrastructure （CNKI）, Wangfang Database and Chinese Biology medicine disc （CBM） were searched for controlled trials and transmission disequilibrium test from establishment of the database to December 2011. Manual retrospective search had been done for important references. According to the inclusion criteria, articles were evaluated by two individual investigators. The quality of included studies were assessed. Cochrane Collaboration＇s RevMan 5.1.1 software was used for data analysis in fixed/random models. Results Six articles including 10 independent studies were enrolled into this analysis, and there was publication bias among the studies. The results of meta-analysis showed, （1）C-2578A＇s allele C significantly increased the susceptibility of CHD in subjects with DiGeorge syndrome（OR = 1.40, 95% CI： 1.04 -1.16） ; G-1154A＇s allele G had the same effect in subjects with DiGeorge syndrome（ OR = 1.87, 95% CI： 1.27 -2.75） ; whereas G-634C＇s allele G significantly increased the susceptibility of CHD in normal subjects（OR = 1.29, 95% CI： 1.02 - 1.62）. （2）G-1154A＇s genotype （AA ＋ AG） was the risk factor increasing the susceptibility of CHD in subjects with DiGeorge syndrome significantly （ OR = 2.10, 95 % CI： 1.32 - 3.34）. （3）Haplotype AAG significantly increased the susceptibility of CHD in subjects with DiGeorge syndrome （OR = 1.82, 95% CI： 1.31 -2.54） ; however, haplotype CGC significantly decreased the susceptibility of CHD in population without DiGeorge syndrome （ OR = 0.79, 95% C1：0.63 - 0.99）. Conclusions The allele, genotype and haplotype of vascular endothelial growth factor were identified out the association with susceptibility of CHD, and there were differences between CHD with or without DiGeorge syndrome. Specific haplotype （ CGC ） had significant protective effects of reducing the risk for CHD in the population without DiGeorge syndrome, but its underlying mechanisms need futher investigation.