Mitochondrial coding and control region variants are associated with Type-2 Diabetes in Pakistani population

Abstract

Background Sequence changes of human mitochondrial DNA (mtDNA) are involved in many human diseases. Mitochondrial DNA variants have been associated with development of type 2 diabetes, which is becoming more prevalent in the Pakistani population. We conducted a case-control study to investigate the role of mtDNA variants associated with diabetes in the Pakistani population. Results Analysis of the HVS2 region showed two variants m.309_310insCT and m.315dup were associated with diabetes. By analyzing complete mtDNA, no variant was found to have significantly different distribution between groups. However, comparison of our diabetic samples’ variants with 1000 Genome Project variants showed eight highly significant variations in mitochondrial genome, four in non-coding region i.e. (m.513G > A, m.195T > C, m.16189T > C, m.16265A > C) and four in coding regions i.e. m.9336A > G (CO-III gene), m.11935T > C (ND4 gene), m.14766C > T (CYB gene) and m.7193T > C (CO-I gene) the last one being a rare mitochondrial variant also. We also found one novel variant m.570C > CACCC in the diabetic group. Conclusion We found specific variations in the mitochondrial genome are associated with type 2 diabetes in the Pakistani patients. These findings suggest that mtDNA variations may play a role in the development of type 2 diabetes in the Pakistani population.