Chen Linan, Jiang Jun, Yao Jialing, Lu Ying, Zhang Xiaolong, Zhang Mingzhi, Zhang Qiu, Peng Hao
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.
Department of Tuberculosis Control, Suzhou Center for Disease Control and Prevention, Suzhou, China.
Front Neurol. 2023 Mar 31;14:1103374. doi: 10.3389/fneur.2023.1103374. eCollection 2023.
As the physical activator of natriuretic peptides, corin has been associated with stroke, but the underlying mechanism is not very clear. Here, we examined whether the promoter's methylation, an epigenetic DNA modification, was associated with the risk of stroke in two independent samples.
A total of 1771 participants including 853 stroke cases and 918 healthy controls were included as a discovery sample and 2,498 community members with 10 years of follow-up were included as a replication sample. DNA methylation of the promoter was quantified by target bisulfite sequencing in both samples. We first examined the single CpG association, followed by a gene-based analysis of the joint association between multiple CpG methylation and stroke, adjusting for conventional risk factors.
The single CpG association analysis found that hypermethylation at all of the 9 CpG sites assayed was significantly associated with lower odds of prevalent stroke in the discovery sample (all < 0.05), and three of them located at Chr4:47840038 (HR = 0.74, = 0.015), Chr4:47839941 (HR = 0.80, = 0.047), and Chr4:47839933 (HR = 0.82, = 0.050) were also significantly associated with incident stroke in the replication sample. The gene-based association analysis found that DNA methylation of the 9 CpG sites at the promoter was jointly associated with stroke in both samples (all < 0.05).
DNA methylation levels of the gene promoter were lower in stroke patients and predicted a higher risk of incident stroke in Chinese adults. The underlying causality warranted further investigation.
作为利钠肽的物理激活剂，corin与中风有关，但其潜在机制尚不清楚。在此，我们在两个独立样本中研究了启动子甲基化（一种表观遗传DNA修饰）是否与中风风险相关。
共有1771名参与者被纳入发现样本，其中包括853例中风病例和918名健康对照，另有2498名有10年随访的社区成员被纳入复制样本。在两个样本中通过靶向亚硫酸氢盐测序对启动子的DNA甲基化进行定量。我们首先检查单个CpG关联，然后对多个CpG甲基化与中风之间的联合关联进行基于基因的分析，并对传统风险因素进行调整。
单个CpG关联分析发现，在发现样本中，所检测的9个CpG位点的高甲基化均与中风患病率较低显著相关（均<0.05），其中位于Chr4:47840038（HR = 0.74，= 0.015）、Chr4:47839941（HR = 0.80，= 0.047）和Chr4:47839933（HR = 0.82，= 0.050）的三个位点在复制样本中也与中风发病率显著相关。基于基因的关联分析发现，启动子处9个CpG位点的DNA甲基化在两个样本中均与中风联合相关（均<0.05）。
中风患者中基因启动子的DNA甲基化水平较低，且在中国成年人中预测了更高的中风发病风险。潜在的因果关系值得进一步研究。
