Combined glutathione S-transferase T1 and M1 positive genotypes afford protection against type 2 diabetes in Japanese.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hori
Masaharu
M
Kumamoto University, Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Oe-honmachi 5-1, Kumamoto, 862-0973, Japan.
Oniki
Kentaro
K
Ueda
Kentaro
K
Goto
Shuji
S
Mihara
Shuichi
S
Marubayashi
Toru
T
Nakagawa
Kazuko
K
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1