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

Abstract

Introduction: 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. Materials & 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. Conclusion: 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.

Keywords: :

• genetic polymorphism
• glutathione S-transferase
• smoking
• Type 2 diabetes

Acknowledgements

We gratefully thank the staff of the Japanese Red Cross Kumamoto Health Care Center for their clinical support, as well as Keiji Takata, Tomoko Yokoyama, Rie Nagata and Hiroko Shindo for their valuable contributions.

Financial disclosure

This work was supported by a Grant-In-Aid (No.16590438 and 19790428) for scientific research from the Japanese Ministry of Education, Science, Sports and Culture. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The author states that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by a Grant-In-Aid (No.16590438 and 19790428) for scientific research from the Japanese Ministry of Education, Science, Sports and Culture. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.