TNF-α基因多态性与妊娠期糖尿病相关性的meta分析

Relationship between TNF-α gene polymorphism and gestational diabetes mellitus:a meta analysis

目的通过meta分析方法评估肿瘤坏死因子α(TNF-α)基因多态性与妊娠期糖尿病(GDM)的相关性。方法以妊娠期糖尿病组和正常对照组基因分布的比值比(OR)为统计量,应用Rev Man5.1软件对多中心研究结果进行异质性检验和数据合并,并对合并结果进行敏感性分析,判断结果的稳定性。结果各研究结果间异质性较大。按照地域差异合并数据,进行亚组分析发现,GDM组和正常对照组TNF-α启动子基因型(GA+AA)/GG出现的OR值,国外人群差异不明显,国内人群差异明显(P<0.000 1),GA+AA基因型出现频率高于对照组;等位基因G/A的出现频率,国外人群差异不明显,国内人群差异仍十分明显(P<0.000 1),GDM组A等位基因出现频率较对照组高。按照(GA+AA)/GG分组合并数据,进行亚组分析发现,国外人群GA+AA组HOMA-IR较GG组低(P<0.000 01),国内人群GA+AA组HOMA-IR较GG组高(P<0.000 1),此外,国内人群GA+AA组TNF-α水平较GG组高(P<0.000 1)。结论 TNF-α基因多态性与GDM相关性存在地域性差异,国内人群TNF-α基因多态性与GDM存在相关性,等位基因A是发生GDM的危险因子;尚无证据证明国外人群TNF-α基因多态性与GDM存在相关性。

Objective To explore the relevance of TNF-α gene polymorphism and gestational diabetes mellitus （GDM）by meta analysis.Methods Taking the gene distribution ratio （OR value）of GDM patients and normal controls as a statistic,the software RevMan5.1 was used to conduct the heterogeneity tests and data consolidation of multi-center studies.Then the combined results were used to conduct the sensitivity analysis and evaluate the stability of results.Results There was a large heterogeneity between the results of several studies.After merging data according to geographical differences,subgroup analysis showed that the TNF-α promoter genotype （GA ＋ AA）/GG frequency（OR value）and the frequency of allele G/A were significantly different between GDM group and normal control group in domestic populations（P ＜0.000 1）,but not in the foreign population,and the frequency of GA ＋ AA genotype and the frequency of allele A were higher in GDM group than in normal control group.After merging data according to （GA ＋ AA）/GG groups,subgroup analysis showed that the HOMA-IR in GA ＋ AA group was lower than in GG group in foreign population（P ＜0.000 01）,while the HOMA-IR in GA ＋ AA group was higher than in GG group in domestic population（P ＜0.000 1）,and the TNF-α level was higher in GA ＋ AA group than in GG group （P ＜ 0.000 1）.Conclusion The correlation between TNF-α gene polymorphism and GDM has regional difference.In the domestic population,TNF-α gene polymorphism is correlated with GDM,and the allele A is a risk factor for the occurrence of GDM.There is no evidence to prove that TNF-α gene polymorphism is correlated with GDM in foreign crowd.