Genetic Association Study of C5178A and G10398A Mitochondrial DNA Variants with Type 2 Diabetes in Bangladeshi Population

The mitochondrial DNA (mtDNA) G10398A variation (Ala -> Thr) within the NADH dehydrogenase (ND3) subunit of complex I of the electron transport chain and C5178A within NADH dehydrogenase subunit (ND1-237, Leu -> Met), have emerged as variations of clinical significance in disorders like type 2 diabetes (T2D). This study aims to explore the relationship of mtDNA C5178A and G10398A variations with T2D in Bangladeshi population. A total of 249 unrelated Bangladeshi populations (127 T2D and 122 healthy controls) were enrolled in this study. Specific DNA sequences within mitochondria were amplified by PCR followed by digestion at the polymorphic sites using AluI and DdeI restriction enzymes. Analyses revealed that 66.93% T2D and 59.02% healthy individuals carried the major allele 'G' at 10398 position of the mtGenome; while the minor allele 'A' was present in 33.07% T2D and 40.98% healthy individuals. G10398A polymorphism had no association with the T2D when total participants were considered. However, in male study participants, G10398A polymorphism can potentially be a protective marker for T2D (OR = 0.30, 95% CI: 0.13-0.67, p < 0.01). Further, 96.72% healthy and 89.76% T2D individuals had C5178 allele while 5178A alleles were respectively found in 3.28% and 10.24% of the study participants. Significant association of mtDNA C5178A polymorphism with the risk of T2D was evident in study participants (OR = 3.36, 95% CI: 1.06-10.62, p = 0.02). Moreover, 5178A allele was associated with the increased risk of T2D in males (OR = 9.01, 95% CI: 1.12-72.73, p = 0.01); but not in females. In the current study, we found stratified association of mtDNA C5178A and G10398A variations with T2D in Bangladeshi population.