Serum oxidative stressors levels and association of mtDNA variants with type 2 diabetes mellitus in the Central India population

Background

The mitochondrial genome has a high rate of mutability which plays a major role in pathogenic mutations. These mutations are implicated with mitochondrial dysfunction increasing the vulnerability to Diabetes Mellitus (DM).

Aim

The study aimed to evaluate the changes in oxidative markers and analyse the specific mitochondrial DNA variants that contributed to DM in the central Indian population.

Method

To assess mitogenomic alteration, Sanger sequencing was used to identify the single nucleotide polymorphisms (SNPs) or variants, while ELISA kits were used to evaluate oxidative stress.

Results

The levels of 8-Hydroxy-2-deoxyguanosine (8-OHdG) and Malondialdehyde (MDA) in type 2 diabetes mellitus (T2DM) were significantly higher than in healthy individual (HI). In T2DM (3371.80 ± 1110.7 pg/ml) the levels of 8-OHdG were significantly greater and were found to be nine times higher compared to the control group (P < 0.001). Additionally, MDA level which is indicative of lipid peroxidation, in the diabetic groups (39.34 ± 23.05 ng/ml) contributed to 18 times higher than the control groups (2.16 ± 2 ng/ml). Moreover, 52 variants were found in our population, among which C10400T variants were significantly prevalent and clustered with the A10398G. These variants confirmed a strong association, on analysis for linkage disequilibrium (r²), with a slightly higher r² value in the T2DM group (0.92) compared to controls (0.85), indicating a stronger link with diabetes. According to multivariate regression analysis, variants associated with the mitogenome such as C16192T (CI: 0.004 to 1.30, p = 0.028) were found to play a protective role against T2DM. Furthermore, A3384G and G16129A may contribute to the protective role against the risk of developing diabetes.

Conclusion

The study demonstrates that diabetic patients are more vulnerable to certain mtDNA variants, directly linked to increased hyperglycemia. Elevated free radical-mediated oxidative stress likely affects these mtDNA variants.