Glutathione S-transferase M1, T1 and P1 gene polymorphisms and the risk of developing type 2 diabetes mellitus in Egyptian diabetic patients with and without diabetic vascular complications

Abstract

Background and aim of work: Persistent oxidative stress is one of several factors that
participate in the pathogenesis of type 2 diabetes mellitus (T2DM). Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that exert important antioxidant roles in the elimination of reactive oxygen species. We aimed to assess the association of genetic polymorphisms in the GST isoenzymes M1, T1 and P1 with the risk of developing T2DM and its vascular related complications in Egyptian diabetic patients.
Subjects and methods: Fifty-four T2DM patients of whom twenty-seven were suffering from vascular complications were compared to fifty-one healthy volunteers. Null genotypes in the GST M1 and T1 genes were screened using polymerase chain reaction (PCR). The A313G single nucleotide polymorphism in the GSTP1 gene was detected using PCR–restriction fragment length polymorphism.
Results: No significant differences were noted between diabetic cases and control group regarding frequencies of null genotypes of GSTM1 and GSTT1 genes (χ²p=0.631 and χ²p= 0.832, respectively). Furthermore, both null genotypes were not associated with the risk of developing T2DM or its related vascular complications whether alone or in combination. The frequency of the heterozygous mutation (AG) in the A313G GSTP1 polymorphism among diabetic cases with and diabetic cases without vascular complications was significantly higher compared to the control group (p=0.023). The risk of developing T2DM was significantly higher in cases presenting with combined heterozygous GSTP1 and null GSTM1 genotypes (Odds ratio= 6.285, 95% confidence interval =1.184–33.347, p=0.021).

Conclusion: Our results could point out to potential roles of GSTP1 polymorphism alone or combined with GSTM1 gene polymorphism in the pathogenesis of T2DM related oxidative stress. Screening for other functional GST gene polymorphisms is important to understand the impact of interaction of multiple genetic factors in the pathogenesis of T2DM.