Korean Diabetes Journal 2005;29(4):315-321.
Published online July 1, 2005.
Glutathion S-Transferase M1 Gene Polymorphism is Associated with Type 2 Diabetic Nephropathy.
Jae Hyeon Kim, Min Kyong Moon, Sang Wan Kim, Hyoung Doo Shin, Young Hwan Hwang, Curie Ahn, Hak Cheol Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee
1Department of Internal Medicine, Seoul National University Boramae Hospital, Korea.
2Genome Research Center for Diabetes and Endocrine Disease, Clinical Research Institute, Seoul National University Hospital, Korea.
3Department of Endocrinology and Metabolism, Seoul National University College of Medicine, Korea.
Abstract
BACKGROUND
Oxidative stress may be a determinant of the development of diabetic nephropathy. Glutathione S-transferases(GST) can work as an endogenous antioxidant to protect cells from oxidative stress. Homozygous deletion of the mu and theta subclasses of GST(GST-M1 and GST-T1), and Val105Ile polymorphism of the pi subclass of GST(GST-P1) are associated with antioxidant enzyme activity. In this study, whether the Val105Ile of GST-P1, null genotype of GST-M1 and GST-T1 are associated with type 2 diabetic nephropathy were examined. METHODS: These GST subclasses were genotyped in 361 type 2 diabetic patients with retinopathy; the subjects were divided into two groups, those with an end stage renal disease(ESRD)(the case group n=177) and those(the control group, n=184) showing no signs of renal involvement. RESULTS: The frequencies of the GST-P1 Ile105Val and GST-T1 null genotypes were no different between the cases and controls. However, the frequency of the GST-M1 null genotype was significantly higher in the cases than the controls(61.7% vs. 51.1%, chi-square=4.09, P=0.043), which was still significant after correction for age, sex and duration of diabetes (P= 0.044). In addition, the GST-M1 null genotype showed an increased frequency between the controls and the cases with long and short durations of type 2 diabetes until the onset of ESRD(51.1, 58.9 and 65.5%, respectively; chi-square for trend=5.12, P=0.024). CONCLUSION: This is the first study to suggest that the GST-M1 gene polymorphism might contribute to the development of ESRD in type 2 diabetic patients.
Key Words: End stage renal disease, Glutathione S-transferases, Polymorphism, Type 2 diabetes


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