Serum Atrial Natriuretic Peptide, 'NPPA' Promoter Methylation, and Cardiovascular Disease: A 10-year Follow-Up Study in Chinese Adults
Linan Chen,
Jing Li,
Min Zhang,
Qiu Zhang,
Lei Wu,
Ying Lu,
Yan He,
Jun Jiang,
Xiaolong Zhang,
Jianwei Hu,
Yi Ding,
Mingzhi Zhang,
Hao Peng
Affiliations
Linan Chen
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou
Jing Li
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou
Min Zhang
Department of Central Office, Suzhou National New and Hi-tech Industrial Development Zone Center for Disease Control and Prevention, Suzhou
Qiu Zhang
Department of Chronic Disease, Gusu Center for Disease Control and Prevention, Suzhou
Lei Wu
Department of Maternal and Child Health, Suzhou Industrial Park Center for Disease Control and Prevention, Suzhou
Ying Lu
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou
Yan He
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou
Jun Jiang
Department of Tuberculosis Control, Suzhou Center for Disease Control and Prevention, Suzhou
Xiaolong Zhang
Department of Tuberculosis Control, Suzhou Center for Disease Control and Prevention, Suzhou
Jianwei Hu
Department of Central Office, Maternal and Child Health Bureau of Kunshan, Suzhou
Yi Ding
Department of Preventive Medicine, College of Clinical Medicine, Suzhou Vocational Health College, Suzhou
Mingzhi Zhang
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou
Hao Peng
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou
Background: Atrial natriuretic peptide (ANP) has been associated with cardiovascular disease (CVD) and related risk factors, but the clinical application is limited and the underlying mechanisms are not very clear. Here, we aimed to examine whether proANP and its coding gene methylation were associated with CVD in the Chinese population. Methods: Serum proANP and peripheral blood DNA methylation of natriuretic peptide A gene ('NPPA') promoter was quantified at baseline for 2,498 community members (mean aged 53 years, 38% men) in the Gusu cohort. CVD events were obtained during 10 years of follow-up. A competing-risks survival regression model was applied to examine the prospective associations of proANP and 'NPPA' promoter methylation with incident CVD. Results: During follow-up, 210 participants developed CVD events, 50 participants died from non-cardiovascular causes, and 214 participants were lost. Per 1-nmol/L increment of serum proANP was associated with a 22% (HR = 1.22, 95%CI: 1.03–1.44, 'P' = 0.025) higher risk of CVD during follow-up. Of the 9 CpG sites assayed, per 2-fold increment of DNA methylation at CpG3 (located at Chr1:11908299) was significantly associated with a half lower risk of CVD (HR = 0.50, 95%CI: 0.30–0.82, 'P' = 0.006). The gene-based analysis found that DNA methylation of the 9 CpGs at 'NPPA' promoter as a whole was significantly associated with incident CVD ('P' < 0.05). Conclusions: Increased proANP and hypomethylation at 'NPPA' promoter at baseline predicted an increased future risk of CVD in Chinese adults. Aberrant DNA methylation of the 'NPPA' gene may participate in the mechanisms of CVD.
