Atrial fibrillation is associated with accumulation of aging-related common type mitochondrial DNA deletion mutation in human atrial tissue.
OBJECTIVE
Accumulation of somatic mutations of mitochondrial DNA (mtDNA) contributes to the aging process and progressive organ dysfunction. We investigated the mitochondrial DNA with 4977-base-pair mtDNA deletion mutation (mtDNA(4977)) in human atrial tissue and correlated the amount of mtDNA(4977) to clinical atrial fibrillation (AF).


RESULTS
Atrial tissue from the right atrial appendage was obtained in 88 patients during open-heart surgery (22 children/adolescents and 66 adults). The amount of mtDNA(4977) was measured using a nested polymerase chain reaction protocol and normalized to wild-type mtDNA. We found that the mtDNA(4977) was absent in all 22 pediatric/adolescent patients. In the adult group, the relative amount of mtDNA(4977) was significantly higher in patients with AF than in patients without AF (0.55 +/- 0.26 vs 0.35 +/- 0.29, p < 0.007) [mean +/- SD]. The amount of mtDNA(4977) was also positively associated with age (r = 0.29, p < 0.01). Left and right atrial pressures, left atrial dimension, hypertension, and cardiac diagnosis did not influence the amount of mtDNA(4977) significantly. Further multivariate analysis showed that both aging and AF contributed independently to the accumulation of mtDNA(4977).


CONCLUSIONS
AF is associated with an increase of mtDNA(4977). This change is similar to the aging process of atrial tissue and might contribute to atrial dysfunction in AF.
Lai
Ling-Ping
LP
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei. Taiwan.
Tsai
Chien-Chen
CC
Su
Ming-Jai
MJ
Lin
Jiunn-Lee
JL
Chen
Yih-Sharng
YS
Tseng
Yung-Zu
YZ
Huang
Shoei K Stephen
SK
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics*; D020029:Base Pairing / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005260:Female; D006325:Heart Atria / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D004272:DNA, Mitochondrial