Investigating GSTT1 and GSTM1 null genotype as the risk factor of diabetes type 2 retinopathy

Abstract

Background: Diabetes is one of the multifactorial disorders with genetics and environmental factors playing important role in its cause. In diabetes, the defects in cellular metabolism results in increasing free radicals. These radicals react with other vital cellular molecules which are responsible in diabetes side effects. Human glutathione S-transferases (GST) are a family of enzymes that catalyses conjugation of electrophilic substances with glutathione. In this research the deletion of two of the most important genes of this family; GSTT1 and GSTM1 genes was investigated as the risk factor for diabetes mellitus type II and one of its most important complications; retinopathy.

Material and methods: In this study deletion of GSTT1 and GSTM1 genes in 57 diabetics' patients with retinopathy and 58 diabetic peoples without retinopathy was examined. DNA was extracted from peripheral blood and then multiplex PCR was performed following agarose gel electrophoresis to detect GSTT1 and GSTM1 null genotypes. Data were analyzed with SPSS v16 software.

Results: The results indicated that there was significant relationship between GSTM1 null genotype with retinopathy side effect of diabetes type 2. While there was no significant relationship between GSTT1 null genotypes with retinopathy in diabetes type 2.

Conclusion: Significant correlation between GSTM1 null genotype and retinopathy in this and other studies could indicate this fact that impair cellular metabolism result in increase free radicals and oxidative pressure. Therefore, GST null genotypes may result in decrease antioxidant capacity which causes side effects of diabetes. Considering the performance of different classes of GST null genotypes additional studies are required to confirm this study.

Figure 1

Gel electrophoresis showing PCR products of GSTT1, GSTM1 and b-globin. L; Molecular weight marker. N; Negative control. T+/M+; DNA from patients with positive GSTM1, GSTT1, and β-globin alleles. T-/M-; Double null genotype of GSTM1 and GSTT1 (in the presence of β-globin PCR product). T+/M-; GSTT1 null/GSTM1 positive. T-/M+; GSTT1 positive/ GSTM1 null.