Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.
Department of Chronic Disease Management, Center for Disease Prevention and Control of Wujiang District, Suzhou, China.
Obes Facts. 2022;15(2):257-270. doi: 10.1159/000521295. Epub 2021 Dec 7.
Atrial natriuretic peptide plays a potential role in obesity with unclear molecular mechanisms. The objective of this study was to examine the association between its coding gene (natriuretic peptide A [NPPA]) methylation and obesity.
Peripheral blood DNA methylation of NPPA promoter was quantified at baseline by targeted bisulfite sequencing for 2,497 community members (mean aged 53 years, 38% men) in the Gusu cohort. Obesity was repeatedly assessed by body mass index (BMI) and waist circumference (WC) at baseline and follow-up examinations. The cross-sectional, longitudinal, and prospective associations between NPPA promoter methylation and obesity were examined.
Of the 9 CpG loci assayed, DNA methylation levels at 6 CpGs were significantly lower in participants with central obesity than those without (all p < 0.05 for permutation test). These CpG methylation levels at baseline were also inversely associated with dynamic changes in BMI or WC during follow-up (all p < 0.05 for permutation test). After an average 4 years of follow-up, hypermethylation at the 6 CpGs (CpG2 located at Chr1:11908348, CpG3 located at Chr1:11908299, CpG4 located at Chr1:11908200, CpG5 located at Chr1:11908182, CpG6 located at Chr1:11908178, and CpG8 located at Chr1:11908165) was significantly associated with a lower risk of incident central obesity (all p < 0.05 for permutation test).
Hypomethylation at NPPA promoter was associated with increased future risk of central obesity in Chinese adults. Aberrant DNA methylation of the NPPA gene may participate in the mechanisms of central obesity.
心钠肽在肥胖中发挥着潜在作用，但其分子机制尚不清楚。本研究旨在探讨其编码基因（心钠肽 A [NPPA]）甲基化与肥胖之间的关系。
在姑苏队列中，对 2497 名社区成员（平均年龄 53 岁，38%为男性）的外周血 NPPA 启动子 DNA 甲基化进行了靶向亚硫酸氢盐测序，以基线进行定量分析。通过 BMI 和腰围（WC）在基线和随访检查中反复评估肥胖。研究了 NPPA 启动子甲基化与肥胖的横断面、纵向和前瞻性关联。
在所检测的 9 个 CpG 位点中，中心性肥胖参与者的 6 个 CpG 位点的 DNA 甲基化水平明显低于无中心性肥胖者（所有 P 值均 <0.05，经置换检验）。这些 CpG 甲基化水平在基线时也与随访期间 BMI 或 WC 的动态变化呈负相关（所有 P 值均 <0.05，经置换检验）。随访平均 4 年后，6 个 CpG 位点（位于 Chr1：11908348 的 CpG2、位于 Chr1：11908299 的 CpG3、位于 Chr1：11908200 的 CpG4、位于 Chr1：11908182 的 CpG5、位于 Chr1：11908178 的 CpG6 和位于 Chr1：11908165 的 CpG8）的高甲基化与中心性肥胖的发生风险降低显著相关（所有 P 值均 <0.05，经置换检验）。
NPPA 启动子的低甲基化与中国成年人中心性肥胖的未来风险增加相关。NPPA 基因的异常 DNA 甲基化可能参与了中心性肥胖的发生机制。
