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.


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.
Marín-García
José
J
Molecular Cardiology and Neuromuscular Institute, Highland Park, New Jersey 08904, USA.
Zoubenko
Oleg
O
Goldenthal
Michael J
MJ
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D017354:Point Mutation
D004272:DNA, Mitochondrial