Null genotypes of GSTM1 and GSTT1 contribute to increased risk of diabetes mellitus: A meta-analysis

Abstract Diabetes mellitus (DM) is a common disease which results from various causes including genetic and environmental factors. Glutathione S-Transferase M1 ( GSTM1 ) and Glutathione S-Transferase T1 ( GSTT1 ) genes are polymorphic in human and the null genotypes lead to the absence of enzyme function. Many studies assessed the associations between GSTM1/GSTT1 null genotypes and DM risk but reported conflicting results. In order to get a more precise estimate of the associations of GSTM1/GSTT1 null genotypes with DM risk, we performed this meta-analysis. Published literature from PubMed, Embase and China Biology Medicine (CBM) databases was searched for eligible studies. Pooled odds ratios (OR) and corresponding 95% confidence intervals (95%CI) were calculated using a fixed- or random-effects model. 11 publications (a total of 2577 cases and 4572 controls) were finally included into this meta-analysis. Meta-analyses indicated that null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 were all associated with increased risk of DM ( GSTM1 : OR random-effects  = 1.60, 95%CI 1.10–2.34, P OR  = 0.014; GSTT1 : OR random-effects  = 1.47, 95%CI 1.12–1.92, P OR  = 0.005; GSTM1–GSTT1 : OR fixed-effects  = 1.83, 95%CI 1.30–2.59, P OR  = 0.001). Subgroup by ethnicity suggested significant associations between null genotypes of GSTM1 and GSTT1 and DM risk among Asians ( GSTM1 : OR random-effects  = 1.77, 95%CI 1.24–2.53, P OR  = 0.002; GSTT1 : OR random-effects  = 1.58, 95%CI 1.09–2.27, P OR  = 0.015). This meta-analysis suggests null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 are all associated with increased risk of DM, and null genotypes of GSTM1/GSTT1 and dual null genotype of GSTM1–GSTT1 are potential biomarkers of DM.