Risk Prediction of Type 2 Diabetes Mellitus (T2DM) in Indian Families Using Antioxidant Gene Variants

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease that is caused by insulin dysfunction. It is an output of oxidative stress that results from defective redox reactions and increased reactive metabolites (RMs) and is neutralized by antioxidant enzymes. It has been reported that decreased levels of antioxidant enzymes are due to genetic alterations in the respective genes. Therefore, the present study has undertaken a genetic analysis of antioxidant genes and their interaction in the family to assess T2DM risk. Objective: This study aimed to investigate the individual susceptibility/risk to T2DM using antioxidant gene variants and their interactions in family members with a diabetic history. Methods: Genotypic analysis of antioxidant genes was done by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP), haplotype analysis, and gene-gene interactions using statistical tools. Pedigrees were constructed by face-to-face interviews with members of nine families. Results: Genotypes AT (CAT-21A>T), IV (GSTP1+313(105I>V), and CT (GPx1 +599C>T) were found to be frequent in diabetic individuals. For instance, in one family, if only the mother had diabetes, all siblings were found to have the risk genotypes AT (CAT- 21A>T) and CT (GPx1 +599C>T) with 2.12- and 2.11-folds risk of developing T2DM. The risk haplotypes, NNV (GSTM1 N>P(Null>Present), GSTT1 N>P(Null>Present), GSTP1105I>V and TCC (CAT-21A>T, SOD2+47C>T, GPx1+599C>T) were observed in most of the diabetic individuals and non-diabetics possessing the risk haplotypes manifested altered BMI. Conclusion: The present study suggests that the GSTP1105I>V, CAT-21A>T, SOD2+47C>T and GPx1+599C>T gene variants can be prognostic biomarkers for the assessment of T2DM risk in healthy individuals.