SPECIFIC MITOCHONDRIAL-DNA DELETIONS IN IDIOPATHIC DILATED CARDIOMYOPATHY

Objective: Structural changes in human mitochondrial DNA (mtDNA) have been implicated in a number of clinical conditions with dysfunctions i n oxidative phosphorylation called OX-PHOS diseases, some of which hav e cardiac involvement. The objective of this study was to assess the f requency and extent of specific mitochondrial DNA deletions in idiopat hic dilated cardiomyopathy. Methods: DNA extracted from tissue derived from the left ventricle of 41 patients with idiopathic dilated cardio myopathy and 17 controls was amplified by polymerase chain reaction us ing specific primers to assess the incidence and proportion of 5-kb an d 7.4-kb deletions in mitochondrial DNA. Results: In reactions using p rimers to detect the 5-kb deletion, an amplified product of 593 bp was found in low abundance relative to undeleted mitochondrial DNA but wi th high frequency in a number of controls and patients. A second delet ion of 7.4 kb in size was also frequently present in controls and pati ents. In contrast to previous reports, these deletions were found to b e present in both controls and in cardiomyopathic patients, 18 years a nd younger, including several infants. The 7.4-kb deletion was promine ntly increased in both frequency and in its proportion relative to und eleted mitochondrial DNA in patients 40 years and older with idiopathi c dilated cardiomyopathy. Conclusions: At variance with current litera ture our study reports a significant presence of both 5 and 7.4-kb del etions in the young and a higher frequency and quantity of the 7.4-kb deletion in the older cardiomyopathic patients in comparison with cont rols. The increased accumulation of the 7.4-kb deletion as both a func tion of aging and cardiomyopathy is suggestive that this specific mito chondrial DNA deletion arises more likely as an effect of heart dysfun ction rather than as a primary cause of cardiomyopathy.