母亲甲硫氨酸合成酶A2756G及其还原酶A66G基因多态性与子代神经管缺陷易感性关系的Meta分析

Associations of maternal methionine synthase A2756G and methionine synthase reductase A66G polymorphisms with neural tube defects of the offspring: A meta-analysis

目的应用Meta分析方法定量评价母亲甲硫氨酸合成酶(MTR)基因A2756G和甲硫氨酸合成酶还原酶(MTRR)基因A66G多态性与子代神经管畸形(NTDs)易感性的相关性。方法制定检索策略和文献纳入排除标准,系统检索中国生物医学文献数据库、中文科技期刊数据库、中国期刊全文数据库、万方数据库和PubMed、Webof Science外文数据库中自1990年1月到2011年10月的有关MTR A2756G和MTRR A66G位点多态性与子代NTDs易感性的病例对照研究、学位论文及其引文。采用RevMan5.0软件对各文献进行异质性检验和Meta分析,得到合并后的OR值及其95%CI。结果共有18篇文献纳入Meta分析,MTR A2756G(907例病例和1 978例对照)和MTRR A66G(1 123例病例和1 700例对照)基因多态性的文献各11篇。Meta分析结果显示,母亲MTR基因A2756G位点各遗传模型与子代NTDs易感性之间关联性无统计学意义,而MTRR基因A66G位点GG/AG vsAA、GG vs AA、AG vs AA、GG vs AG/AA和G vs A各遗传模型与子代NTDs易感性之间关联性均有统计学意义,OR值及95%CI分别为1.89(1.28～2.78)、1.68(1.31～2.16)、1.77(1.18～2.66)、1.28(1.06～1.55)和1.35(1.12～1.63)。结论母亲MTRR基因A66G位点多态性是子代NTDs发病的重要危险因素之一。

Objective To evaluate associations of maternal methionine synthase （MTR） A2756G and methionine syn- thase reductase（MTRR） A66G polymorphisms with the offspring＇s risk for neural tube defects （NTDs）. Methods The retrieval strategy and criteria for inclusion and exclusion were made. Literature was identified by searches for case- control studies on maternal MTR A2756G or MTRR CJ66A polymorphism and risk of NTDs in the offspring published in English or Chinese from following databases： China Biology Medical Literature Database（ CBM）, Database of Chinese Scientific and Technical Periodicals（ VIP）, China National Knowledge Infrastructure（ CNKI）, Digital Journal Full-text Database（ CHINAINFO）, PubMed and Web of Science from January 1990 to October 2010. Combined OR values and 95% CI were calculated with Review Manager 5.0. Results 18 eligible studies were included in the meta-analysis, among which 11 studies（907 cases and 1,978 controls） on maternal MTR A2756G polymorphism, and 11 （ 1 123 casesand 1 700 controls） on maternal MTRR A66G polymorphism. Statistical analysis of the combined data showed that there was no significant association between maternal MTR A2756G polymorphism and the risk of NTDs, while there were significant associations between maternal MTRR A66G polymorphism and the risk of NTDs in GG/AG vs. AA, GG vs. AA, AG vs. AA, GG vs. AG/AA and G vs. A genetic models, and their pooled OR values and 95% C/were 1.89 （ 1.28-2.78 ）, 1.68 （ 1.31-2.16）, 1.77 （ 1.18-2.66 ）, 1.28 （ 1.06-1.55 ） and 1.35 （ 1.12-1.63 ）, respectively. Conclusion Maternal MTRR A66G polymorphism is a risk factor for NTDs.