Association between NPPA promoter methylation and hypertension: results from Gusu cohort and replication in an independe
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RESEARCH
Open Access
Association between NPPA promoter methylation and hypertension: results from Gusu cohort and replication in an independent sample Jing Li1†, Jinhua Zhu2†, Liyun Ren1, Shengqi Ma1, Bin Shen2, Jia Yu1, Rongyan Zhang2, Mingzhi Zhang1, Yan He1,3 and Hao Peng1,3*
Abstract Background: Atrial natriuretic peptide (ANP), one of the main members of the natriuretic peptides system, has been associated with hypertension and related complications, but the underlying molecular mechanisms are not very clear. Here, we aimed to examine whether DNA methylation, a molecular modification to the genome, of the natriuretic peptide A gene (NPPA), the coding gene of ANP, was associated with hypertension. Methods: Peripheral blood DNA methylation of NPPA promoter was quantified by target bisulfite sequencing in 2498 community members (mean aged 53 years, 38% men) as a discovery sample and 1771 independent participants (mean aged 62 years, 54% men) as a replication sample. In both samples, we conducted a single CpG association analysis, followed by a gene-based association analysis, to examine the association between NPPA promoter methylation and hypertension, adjusting for age, sex, education level, cigarette smoking, alcohol consumption, obesity, fasting glucose, and lipids. Multiple testing was controlled by the false discovery rate approach. Results: Of the 9 CpG loci assayed, hypermethylation at 5 CpGs (CpG1, CpG3, CpG6, CpG8, and CpG9) was significantly associated with a lower odds of prevalent hypertension in the discovery sample, and one CpG methylation (CpG1 located at Chr1:11908353) was successfully replicated in the replication sample (OR = 0.82, 95%CI 0.74–0.91, q = 0.002) after adjusting for covariates and multiple testing. The gene-based analysis found that DNA methylation of the 9 CpGs at NPPA promoter as a whole was significantly associated with blood pressure and prevalent hypertension in both samples (all P < 0.05). (Continued on next page)
* Correspondence: [email protected] † Jing Li and Jinhua Zhu contributed equally to this work and should be considered co-first authors. 1 Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou 215123, China 3 Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China 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 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in
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