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.
- cohort studies
- cardiovascular disease
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Contributors YT, RF and KS discussed interpretation of data and wrote the manuscript. KS designed the study and directed its implementation. YT and SH performed the statistical analysis. HY, EM, HI and KO collected the study data and helped supervise the project. NH collected and provided DNA samples. YT, MY, YA and GM measured DNA methylation. All authors discussed the results, commented on the manuscript and contributed to all take responsibility for it.
Funding This study was supported by the Japan Society for the Promotion of Science (JSPS) under Grants-in-Aid for Scientific Research (Numbers 26293144, 17K09139, 16H06277 and 20K10515).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The protocol for this study was approved by the Ethics Committee of Fujita Health University (Approval No. HG19-069).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. No data are available. The data sets used in this study include personal information.Thus, datasets are available from the corresponding author, Prof.Koji Suzuki, on your reasonable requests.
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