Mutations in the cardiac mitochondrial DNA control region associated with cardiomyopathy and aging.

Background: An age-dependent accumulation of point mutations in the noncoding control region of human mitochondrial D-loop has been found in cultured fibroblasts and muscle cells. Damage in mitochondrial DNA (mtDNA) coding genes and decreased bioenergetic generation have also been found in human cardiac tissues with aging and in cardiac disease.
Methods and Results: We analyzed cardiac mtDNA for the incidence and distribution of point mutations in the D-loop control region involved in mtDNA replication (from nucleotides 110 to 570) in 47 patients with cardiomyopathy and 40 subjects with no history of cardiac disease. The nucleotide changes in the control region were compared with changes in a cytb fragment of roughly the same size in controls and patients. Frequency and distribution of mutations in relation to age and cardiac disease were assessed. No significant accumulation of point mutations in the D-loop control region or in cytb was found as a function of age. However, mutations in important sites within the D-loop control region were present in 8 patients (17%).
Conclusions: We found specific mutations at critical sites in the D-loop in cardiomyopathy that may play a role in cardiac pathogenesis. Age does not appear to be a factor in mutation accumulation.