Global DNA hypermethylation in peripheral blood mononuclear cells and cardiovascular disease risk: A population-based propensity score-matched cohort study

Yoshiki Tsuboi, Hiroya Yamada, Eiji Munetsuna, Ryosuke Fujii, Mirai Yamazaki, Yoshitaka Ando, Genki Mizuno, Hiroaki Ishikawa, Koji Ohashi, Shuji Hashimoto, Nobuyuki Hamajima, Koji Suzuki

Research output: Contribution to journalArticlepeer-review

Abstract

Background: DNA methylation plays an important role in the pathogenesis and progression of cardiovascular disease (CVD) but the prospective association of DNA methylation with CVD has not been evaluated. Here, we conducted a prospective study to examine whether long interspersed nuclear element-1 (LINE-1) DNA methylation is associated with CVD mortality in a Japanese population. Methods: We targeted 822 Japanese who participated in a health check-up in 1990 and had no clinical history of cancer, stroke or ischaemic heart disease. DNA was extracted from peripheral blood mononuclear cells and LINE-1 DNA methylation at three CpG sites was measured using a pyrosequencing method. We used propensity score (PS) matching to reduce the effect of potential confounding. Results: During 18 118.7 persons-years of follow-up, there were 329 deaths from all-causes and 85 deaths from CVD. In PS-matched analysis, a significantly higher HR for CVD mortality was observed in the hypermethylation group than in the hypomethylation group for elderly participants (HR 2.77; 95% CI 1.55 to 4.93). No significant association between LINE-1 DNA methylation and CVD was observed for middle-aged participants. Conclusions: Based on this prospective study, we suggest that LINE-1 DNA hypermethylation is associated with increased CVD mortality risk in an elderly population.

Original languageEnglish
Article numbere215382
JournalJournal of Epidemiology and Community Health
DOIs
Publication statusAccepted/In press - 2021

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Public Health, Environmental and Occupational Health

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