Mitochondrial DNA copy number and incident atrial fibrillation
- PDF / 1,001,852 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 58 Downloads / 191 Views
RESEARCH ARTICLE
Open Access
Mitochondrial DNA copy number and incident atrial fibrillation Di Zhao1, Traci M. Bartz2, Nona Sotoodehnia2, Wendy S. Post1,3, Susan R. Heckbert4, Alvaro Alonso5, Ryan J. Longchamps6, Christina A. Castellani6, Yun Soo Hong1, Jerome I. Rotter7, Henry J. Lin7, Brian O’Rourke8, Nathan Pankratz9, John A. Lane9, Stephanie Y. Yang6, Eliseo Guallar1* and Dan E. Arking6*
Abstract 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). mtDNACN 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. Doseresponse 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. Keywords: Mitochondria DNA copy number, mtDNA, Atrial fibrillation
* Correspondence: [email protected]; [email protected] 1 Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, 2024 E. Monument Street, Room 2-645, Baltimore, MD 21205, USA 6 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Miller Research Building, Room 459, Baltimore, MD 21205, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 Int
Data Loading...
