Combined Glutathione S -transferase T1 and M1 Positive Genotypes Afford Protection Against Type 2 Diabetes in Japanese

Abstract

Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. The aim of this study is to determine the association between the incidence of Type 2 diabetes and gene polymorphisms of glutathione S-transferase (GST), which modulates oxidative stress. The associations between the incidence of Type 2 diabetes and the GSTT1 and GSTM1 genotypes were analyzed in 469 Japanese participants in a health-screening program. The clinical characteristics and smoking status were obtained from the health screening record. The incidence of diabetes was 1.5-fold higher in the GSTT1 and GSTM1 null (-) genotype than the GSTT1 and GSTM1 present (+) genotype, respectively. Although the effect of each null genotype was not significant, the combined GSTT1+/GSTM1+ genotypes conferred a significant reduction in risk of diabetes in comparison with the other combinations of genotypes (adjusted odds ratio [OR]: 0.30; 95% confidence interval [CI]: 0.12-0.71). In stratified analyses by smoking status, the incidence of diabetes was significantly higher in never-smokers with the GSTT1- genotype than those with the GSTT1+ genotype (OR: 2.85; 95% CI: 1.17-6.94) and increased significantly in current smokers (OR: 5.91; 95% CI: 1.96-17.88). The effect of the GSTM1- genotype was significant only in current smokers. This study demonstrated that the GSTT1- and GSTT1-/GSTM1- genotypes are independent risk factors for development of Type 2 diabetes regardless of the smoking status of the patient, and that these genotypes and current smoking were interactively associated with the incidence of Type 2 diabetes.