5，10-亚甲基四氢叶酸还原酶基因C677T多态性与先天性心脏病关系的Meta分析

目的对5，10-亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态性与先天性心脏病（CHD）的相关性研究进行Meta分析。方法制定原始文献的纳入标准及检索策略，检索PubMed、EMBASE、Ovid、Springer、中国期刊全文数据库、维普中文科技期刊数据库、万方数据库和中国生物医学文献数据库（1994年1月至2009年1月）中的文献，收集MTHFR基因C677T多态性与CHD相关性的病例一对照研究，剔除不符合要求的文献，应用RevMan4．2软件进行Meta分析，得出合并后的OR值及其95％CI。结果共18篇文献符合纳入标准进入Meta分析。数据合并结果显示，子代MTHFR基因677位点TT／CC和（TT＋CT）／CC与CHD易感性有统计学意义，OR值（95％CI）分别为1．55（1．24～1．93）和1．23（1．06～1．42），P〈0．05；子代MTHFR基因677位点CT／CC与CHD易感性无统计学意义，OR值（95％CI）为1．15（0．99—1．34），P〉0．05。父亲MTHFR基因677位点TT／CC和（TT＋CT）／CC与子代CHD的易感性有统计学意义，OR值（95％CI）分别为1．84（1．23～2．74）和1．33（1．04～1．71），P〈0．05；父亲MTHFR基因677位点CT／CC与子代CHD易感性无统计学意义，OR值（95％CI）为1．25（0．96～1．62），P〉0．05。母亲MTHFR基因677位点TWCC、CT／CC和（TT＋CT）／CC与子代CHD易感性均无统计学意义，OR值（95％CI）分别为1．20（0．92-1．56）、1．03（0．86～1．24）和1．07（0．90—1．27），P均〉0．05。传递不平衡分析未发现在CHD核心家系的MTHFR基因677位点存在突变的传递不平衡现象，OR值为0．90（95％CI：0．79～1．12），P〉0．05。结论子代MTHFR基因677位点TT和TT＋CT为CHD的危险因素之一；父亲MTHFR基因677位点TT和TT＋CT是子代CHD的危险因素之一；母亲MTHFR基因677位点多态性与子代CHD的发生无关。

Meta-analysis of the association between 5, 10-methylenetetrahydrofolate reductase C677T polymorphisms and congenital heart disease

Objective To evaluate the relationship between 5,10-methylenetetrahydrofolate reductase （MTHFR） gene C677T polymorphisms and congenital heart disease （CHD）. Methods PubMed, EMBASE, Ovid, Springer, China National Knowledge Infrastructure, Vip Chinese Periodical Database, Wanfang Chinese Periodical Database and Chinese Bio-medicine Database were searched for the case-control study on the association of MTHFR gene C677T polymorphisms with CHD from Jan 1994 to Jan 2009. According to inclusion criteria, articles were evaluated. Poor-quality studies were excluded, and RevMan 4.2 software was applied for investigating the heterogeneity among individual studies and calculating the pooled odds ratio （OR） and 95% confidence interval（CI）. Results 18 eligible studies were included. Statistics of the combined data revealed a significant difference between the offsprings with CHD carrying of TT/CC, （ TT ＋ CT）/CC of MTHFR gene C677T and controls, the pooled OR of TT/CC and （ TT ＋ CT）/CC was 1.55 （ 1.24 - 1.93 ） and 1.15 （ 1.06 - 1.42） （ P 〈 0.05 ） ; there was no difference between the offsprings with CHD carrying of CT/CC of MTHFR gene C677T and controls, the pooled OR was 1.15 （0.99 - 1.34 ） （P 〉 0.05 ）. There was a significant difference between the CHD of offspring with paternal TT/CC, （ TT ＋ CT）/CC of MTHFR gene and controls, the pooled OR of TT/CC and （ TT ＋ CT）/CC of MTHFR gene C677T was 1.84（ 1.23 - 2.74） and 1.33 （ 1.04 - 1.71 ）（ P 〈 0.05 ） ; there was no difference between the CHD of offspring with paternal CT/CC of MTHFR gene C677T and controls, the pooled OR was 1.25 （0.96 - 1.62 ） （ P 〉 0.05 ）. There was no association between the CHD of offspring and maternal MTHFR gene C677T, the pooled OR of maternal TT/CC, CT/CC and （TT ＋ CT）/CC was 1.20（0.92 - 1.56）, 1.03 （0.86 - 1.24） and 1.07 （ 0.90 - 1.27 ） （ P 〉 0.05 ） , respectively. The results of transmission disequilibrium test （TDT） analysis showed that no allele transmission disequilibrium of MTHFR gene 677T existed in CHD nuclear families, OR = 0.90,95% CI：0.79 - 1.12 （ P 〉 0.05 ）. Conclusions The results suggested the offspring and paternal MTHFR gene 677TT, 677 （ TT ＋ CT） were both risk factors for the CHD; there was no association between maternal MTHFR gene C677T and onset of CHD in offspring.