Role of DNA methylation on the association between physical activity and cardiovascular diseases: results from the longitudinal multi-ethnic study of atherosclerosis (MESA) cohort.

Autor: Shi H; Department of Clinical and Translational Research, University of Rochester Medical Center, Rochester, NY, 14642-0708, USA.; Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, 14642, USA., Ossip DJ; Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, 14642, USA., Mayo NL; Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, 14642, USA., Lopez DA; Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, 14642, USA., Block RC; Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, 14642, USA., Post WS; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Bertoni AG; Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA., Ding J; Department of Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, 27157, USA., Chen S; Aab Cardiovascular Research Institute, University of Rochester, School of Medicine and Dentistry, Rochester, NY, 14642, USA.; Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, Rochester, NY, 14642, USA., Yan C; Aab Cardiovascular Research Institute, University of Rochester, School of Medicine and Dentistry, Rochester, NY, 14642, USA.; Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, Rochester, NY, 14642, USA., Xie Z; Department of Clinical and Translational Research, University of Rochester Medical Center, Rochester, NY, 14642-0708, USA., Hoeschele I; Department of Statistics, Fralin Life Sciences Institute at Virginia Tech, Blacksburg, VA, 24061, USA., Liu Y; Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, 27701, USA. yongmei.liu@duke.edu., Li D; Department of Clinical and Translational Research, University of Rochester Medical Center, Rochester, NY, 14642-0708, USA. Dongmei_Li@urmc.rochester.edu.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2021 Nov 03; Vol. 22 (1), pp. 790. Date of Electronic Publication: 2021 Nov 03.
DOI: 10.1186/s12864-021-08108-w
Abstrakt: Background: The complexity of physical activity (PA) and DNA methylation interaction in the development of cardiovascular disease (CVD) is rarely simultaneously investigated in one study. We examined the role of DNA methylation on the association between PA and CVD.
Results: The Multi-Ethnic Study of Atherosclerosis (MESA) cohort Exam 5 data with 1065 participants free of CVD were used for final analysis. The quartile categorical total PA variable was created by activity intensity (METs/week). During a median follow-up of 4.0 years, 69 participants developed CVD. Illumina HumanMethylation450 BeadChip was used to provide genome-wide DNA methylation profiles in purified human monocytes (CD14+). We identified 23 candidate DNA methylation loci to be associated with both PA and CVD. We used the structural equation modeling (SEM) approach to test the complex relationships among multiple variables and the roles of mediators. Three of the 23 identified loci (corresponding to genes VPS13D, PIK3CD and VPS45) remained as significant mediators in the final SEM model along with other covariates. Bridged by the three genes, the 2nd PA quartile (β = - 0.959; 95%CI: - 1.554 to - 0.449) and the 3rd PA quartile (β = - 0.944; 95%CI: - 1.628 to - 0.413) showed the greatest inverse associations with CVD development, while the 4th PA quartile had a relatively weaker inverse association (β = - 0.355; 95%CI: - 0.713 to - 0.124).
Conclusions: The current study is among the first to simultaneously examine the relationships among PA, DNA methylation, and CVD in a large cohort with long-term exposure. We identified three DNA methylation loci bridged the association between PA and CVD. The function of the identified genes warrants further investigation in the pathogenesis of CVD.
(© 2021. The Author(s).)
Databáze: MEDLINE
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