Interaction of antioxidant gene variants and susceptibility to Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes is the seventh most common disease leading to death with a global estimate of 425 million diabetics, which is expected to be 629 million in 2045. The role of reactive metabolites and antioxidants, such as glutathione, glutathione peroxidase, superoxide dismutase and catalase in type 2 diabetes mellitus (T2DM) provides an opportunity for identifying gene variants and risk genotypes. We hypothesised that certain antioxidant gene-gene interactions are linked to susceptibility to T2DM and so can model disease risk prediction.

MATERIALS AND METHODS: Genotyping of single nucleotide polymorphisms (SNPs) in antioxidant genes for glutathione (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) was performed in 558 T2DMs and 410 age and sex matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), routine lab indices by standard techniques.

RESULTS: The null/null allele combination of GSTM1del and GSTT1del increased disease risk up to 1.7-fold. The combination of SNPs in GSTM1del,GSTT1del, GSTP1+313A/G and in CAT-21A/T, SOD2+47C/T, GPx1+599C/T increased the risk of diabetes up to 13.5 and 2.1-fold respectively. Interaction of SNPs GSTM1del, GSTT1del, GSTP1+313A/G (105Ile/Val), CAT-21A/T, SOD2+47C/T, GPx1+599C/T showed a highly significant allele combination with disease risk >5x103 fold.

CONCLUSION: As the number of gene combinations increase, there is a rise in odds ratio showing disease risk, suggesting that gene-gene interaction plays an important role in T2DM susceptibility. Individuals who possess the GSTM1del, GSTT1del, GSTP1 105I/V(+313A/G), CAT-21A/T, SOD2+47C/T and GPx1+599C/T are at very high risk of developing T2DM.