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Laboratory and Animal Investigations |

Atrial Fibrillation Is Associated With Accumulation of Aging-Related Common Type Mitochondrial DNA Deletion Mutation in Human Atrial Tissue*

Ling-Ping Lai, MD, PhD; Chien-Chen Tsai, MD; Ming-Jai Su, PhD; Jiunn-Lee Lin, MD; Yih-Sharng Chen, MD; Yung-Zu Tseng, MD; Shoei K. Stephen Huang, MD
Author and Funding Information

*From the Institute of Pharmacology (Drs. Lai and Su), College of Medicine, National Taiwan University; and Departments of Pathology (Dr. Tsai), Internal Medicine (Drs. Lin, Tseng, and Huang), and Surgery (Dr. Chen), National Taiwan University Hospital, Taipei, Taiwan.

Correspondence to: Ming-Jai Su, PhD, Institute of Pharmacology, College of Medicine, National Taiwan University, No 1, Section 1, Jen-Ai Rd, Taipei, Taiwan; e-mail: mjsu@ha.mc.ntu.edu.tw



Chest. 2003;123(2):539-544. doi:10.1378/chest.123.2.539
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Study 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 (mtDNA4977) in human atrial tissue and correlated the amount of mtDNA4977 to clinical atrial fibrillation (AF).

Methods and 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 mtDNA4977 was measured using a nested polymerase chain reaction protocol and normalized to wild-type mtDNA. We found that the mtDNA4977 was absent in all 22 pediatric/adolescent patients. In the adult group, the relative amount of mtDNA4977 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 mtDNA4977 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 mtDNA4977 significantly. Further multivariate analysis showed that both aging and AF contributed independently to the accumulation of mtDNA4977.

Conclusion: AF is associated with an increase of mtDNA4977. This change is similar to the aging process of atrial tissue and might contribute to atrial dysfunction in AF.

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