Table8_Individual and combined effects of the GSTM1, GSTT1, and GSTP1 polymorphisms on type 2 diabetes mellitus risk: A systematic review and meta-analysis.xlsx

Backgrounds: Compared with previously published meta-analyses, this is the first study to investigate the combined effects of glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1 IIe105Val) and type 2 diabetes mellitus (T2DM) risk; moreover, the credibility of statistically significant associations was assessed; furthermore, many new original studies were published.
Objectives: To determine the relationship between GSTM1, GSTT1, and GSTP1 polymorphisms with T2DM risk.
Methods: PubMed, Embase, Wanfang, and China National Knowledge Infrastructure Databases were searched. We quantify the relationship using crude odds ratios and their 95% confidence intervals Moreover, the Venice criteria, false-positive report probability (FPRP), and Bayesian false discovery probability (BFDP) were used to validate the significance of the results.
Results: Overall, significantly increased T2DM risk was found between individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on T2DM risk, but, combined effects of the GSTT1 and GSTP1 polymorphisms was not statistically significant. GSTT1 gene polymorphism significantly increases the risk of T2DM complications, while GSTM1 and GSTP1 polymorphisms had no statistical significance. The GSTM1 null genotype was linked to a particularly increased risk of T2DM in Caucasians; the GSTT1 null genotype was connected to a significantly higher risk of T2DM in Asians and Indians; and the GSTP1 IIe105Val polymorphism was related to a substantially increased T2DM risk in Indians. Moreover, the GSTM1 and GSTT1 double null genotype was associated with substantially increased T2DM risk in Caucasians and Indians; the combined effects of GSTM1 and GSTP1 polymorphisms was associated with higher T2DM risk in Caucasians. However, all significant results were false when the Venice criteria, FPRP, and BFDP test were used (any FPRP >0.2 and BFDP value >0.8).
Conclusion: The current analysis strongly suggests that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms might not be connected with elevated T2DM risk.

背景：与既往已发表的荟萃分析相比，本研究首次探讨了谷胱甘肽S-转移酶（glutathione-S-transferase, GST）基因多态性[涵盖GSTM1、GSTT1及GSTP1 IIe105Val位点]与2型糖尿病（type 2 diabetes mellitus, T2DM）发病风险的联合效应；同时，本研究对统计学显著关联的可信度进行了评估，且纳入了近年新发表的诸多原创研究。
目的：本研究旨在明确GSTM1、GSTT1及GSTP1基因多态性与T2DM发病风险之间的关联。
方法：本研究检索了PubMed、Embase、万方数据知识服务平台及中国知网（China National Knowledge Infrastructure, CNKI）数据库。我们采用粗比值比（crude odds ratio, OR）及其95%置信区间（confidence interval, CI）量化二者间的关联；同时，采用威尼斯标准（Venice criteria）、假阳性报告概率（false-positive report probability, FPRP）以及贝叶斯错误发现概率（Bayesian false discovery probability, BFDP）对研究结果的显著性进行验证。
结果：整体而言，GSTM1、GSTT1及GSTP1基因多态性的单独及联合效应均与T2DM发病风险升高存在显著关联，但GSTT1与GSTP1基因多态性的联合效应未达到统计学显著性。GSTT1基因多态性可显著升高T2DM并发症的发病风险，而GSTM1与GSTP1基因多态性则无统计学意义。在高加索人群中，GSTM1缺失基因型与T2DM发病风险显著升高密切相关；在亚洲人群及印度人群中，GSTT1缺失基因型与T2DM发病风险显著升高相关；而在印度人群中，GSTP1 IIe105Val多态性与T2DM发病风险大幅升高存在关联。此外，在高加索人群及印度人群中，GSTM1与GSTT1双缺失基因型与T2DM发病风险大幅升高相关；在高加索人群中，GSTM1与GSTP1基因多态性的联合效应与T2DM发病风险升高相关。但经威尼斯标准、FPRP及BFDP检验后，所有上述显著关联均为假阳性结果（任意FPRP>0.2且BFDP值>0.8）。
结论：本项分析强烈提示，GSTM1、GSTT1与GSTP1基因多态性的单独及联合效应可能与T2DM发病风险升高并无关联。