Description of Mitochondrial Gene Mutations in Pakistani Patients with Coronary Artery Disease: An Investigation of Genetic Susceptibility

Background: Mutations in mitochondrial DNA (mtDNA) were the important causes of cardiovascular diseases. However, little was known regarding the role of mitochondrial DNA (mt-DNA) mutations in coronary artery disease (CAD). To investigated the association between mitochondrial genes mutations and CAD in Pakistani population. Methods: Approximately, 11 related CAD patients and 29 control subjects were recruited in this study; we performed PCRRFLP to amplify mitochondrial genes and subsequently sequenced the PCR products. In addition, the pathogenicity scoring system was used to evaluate the deleterious roles of these genes mutations. We also used real-time PCR method to determine the mtDNA content in CAD patients carrying these mutations. Results: Three mutations were identified by PCR-Sanger sequencing; these mutations included mt-ND4 12133C>T, mt-ND5 12372G>A and mt-CYB 15884G>C. These mutations were localized at the highly conserved nucleotides, may cause the failure in mt-DNA metabolism. Furthermore, CAD group showed a clear reduction in mitochondrial copy number by comparing with the controls. Conclusions: Mutations in mt-DNA genes were the important causes of CAD, our findings provided novel insight into the pathophysiology of CAD that were manifested by mitochondrial dysfunction.