Background: Mutations in mitochondrial DNA (mtDNA) were the important causes of cardiovascular diseases. However, little was known regarding the role of mitochondrial tRNA (mt-tRNA) mutations in acute Myocardial Infarction (AMI).
Objective: To investigate the association between mt-tRNA mutations and AMI in Han Chinese population.
Methods: 100 unrelated AMI patients and 50 control subjects were recruited in this study; we performed PCR-RFLP to amplify 22 mt-tRNA genes and subsequently sequenced the PCR products. In addition, the pathogenicity scoring system was used to evaluate the deleterious roles of these mt-tRNA mutations. We also used real-time PCR method to determine the mtDNA content in AMI patients carrying these tRNA mutations.
Results: 4 tRNA mutations were identified by PCR-Sanger sequencing; these mutations included tRNAIle A4295G, tRNAMet A4435G, tRNAAla T5655C, tRNALeu (CUN) A12308G. Notably, these mutations were localized at the highly conserved nucleotides of the corresponding tRNAs, may cause the failure in mt-tRNA metabolism. Moreover, AMI group showed a marked reduction in mitochondrial copy number when compared with the controls (P<0.05).
Conclusions: Mutations in mt-tRNA genes were the important causes of AMI, our findings provided novel insight into the pathophysiology of AMI that were manifested by mitochondrial dysfunction.