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Mitochondrial DNA copy number and incident atrial fibrillation.

TitleMitochondrial DNA copy number and incident atrial fibrillation.
Publication TypeJournal Article
Year of Publication2020
AuthorsZhao D, Bartz TM, Sotoodehnia N, Post WS, Heckbert SR, Alonso A, Longchamps RJ, Castellani CA, Hong YSoo, Rotter JI, Lin HJ, O'Rourke B, Pankratz N, Lane JA, Yang SY, Guallar E
Secondary AuthorsArking DE
JournalBMC Med
Date Published2020 Sep 16

BACKGROUND: Mechanistic studies suggest that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown.

METHODS: We conducted prospective analyses of 19,709 participants from the Atherosclerosis Risk in Communities Study (ARIC), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Cardiovascular Health Study (CHS). mtDNA-CN from the peripheral blood was calculated from probe intensities on the Affymetrix Genome-Wide Human single nucleotide polymorphisms (SNP) Array 6.0 in ARIC and MESA and from multiplexed real-time quantitative polymerase chain reaction (qPCR) in CHS. Incident AF cases were identified through electrocardiograms, review of hospital discharge codes, Medicare claims, and death certificates.

RESULTS: The median follow-up time was 21.4 years in ARIC, 12.9 years in MESA, and 11.0 years in CHS, during which 4021 participants developed incident atrial fibrillation (1761 in ARIC, 790 in MESA, and 1470 in CHS). In fully adjusted models, participants with the lowest quintile of mitochondria DNA copy number had an overall 13% increased risk (95% CI 1 to 27%) of incident atrial fibrillation compared to those with the highest quintile. Dose-response spline analysis also showed an inverse association between mitochondria DNA copy number and hazard for atrial fibrillation for all three cohorts. These associations were consistent across subgroups.

CONCLUSIONS: Mitochondria DNA copy number was inversely associated with the risk of AF independent of traditional cardiovascular risk factors. These findings implicate mitochondria DNA copy number as a novel risk factor for atrial fibrillation. Further research is warranted to understand the underlying mechanisms and to evaluate the role of mitochondria DNA copy number in the management of atrial fibrillation risk.

Alternate JournalBMC Med
PubMed ID32933497
PubMed Central IDPMC7493408
Grant ListT32 GM007814 / GM / NIGMS NIH HHS / United States
P30AG021334 / / Claude D. Pepper Older Americans Independence Center, University of California San Francisco /
16EIA26410001 / AHA / American Heart Association-American Stroke Association / United States
K24 HL148521 / HL / NHLBI NIH HHS / United States
R01HL131573 / / Foundation for the National Institutes of Health /