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 in oxidative phosphorylation called OX-PHOS diseases, some of which have cardiac involvement. The objective of this study was to assess the frequency and extent of specific mitochondrial DNA deletions in idiopathic dilated cardiomyopathy.


METHODS
DNA extracted from tissue derived from the left ventricle of 41 patients with idiopathic dilated cardiomyopathy and 17 controls was amplified by polymerase chain reaction using specific primers to assess the incidence and proportion of 5-kb and 7.4-kb deletions in mitochondrial DNA.


RESULTS
In reactions using primers to detect the 5-kb deletion, an amplified product of 593 bp was found in low abundance relative to undeleted mitochondrial DNA but with high frequency in a number of controls and patients. A second deletion of 7.4 kb in size was also frequently present in controls and patients. In contrast to previous reports, these deletions were found to be present in both controls and in cardiomyopathic patients, 18 years and younger, including several infants. The 7.4-kb deletion was prominently increased in both frequency and in its proportion relative to undeleted mitochondrial DNA in patients 40 years and older with idiopathic dilated cardiomyopathy.


CONCLUSIONS
At variance with current literature our study reports a significant presence of both 5 and 7.4-kb deletions in the young and a higher frequency and quantity of the 7.4-kb deletion in the older cardiomyopathic patients in comparison with controls. The increased accumulation of the 7.4-kb deletion as both a function of aging and cardiomyopathy is suggestive that this specific mitochondrial DNA deletion arises more likely as an effect of heart dysfunction rather than as a primary cause of cardiomyopathy.
Marin-Garcia
J
J
Molecular Cardiology Institute, Highland Park, NJ 08904, USA.
Goldenthal
M J
MJ
Ananthakrishnan
R
R
Pierpont
M E
ME
Fricker
F J
FJ
Lipshultz
S E
SE
Perez-Atayde
A
A
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping
D017931:DNA Primers; D004272:DNA, Mitochondrial