Interaction of antioxidant gene variants and susceptibility to type 2 diabetes mellitus

ABSTRACT

Background: Diabetes is the seventh most common disease leading to death with a global estimate of 425 million diabetics, 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 with T2DM and 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 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 were significantly linked with disease risk >5 × 10³ fold.

Conclusion: As the number of gene combinations increase, there is a rise in the odds ratio of 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.

KEYWORDS:

• Type 2 diabetes mellitus
• antioxidants
• gene variants
• gene-gene interaction
• susceptibility

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Acknowledgements

The authors are grateful to the University Grant Commission (UGC), Indian Council of Medical Research, New Delhi and Centre for Excellence, Higher Education, Government of Uttar Pradesh, Lucknow, India, for generous grants. The departmental equipment facility provided by DST-FIST-PURSE is duly acknowledged.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the University Grants Commission.