DNA methylation of the natriuretic peptides system genes and ischemic stroke: gene-based and gene-set analyses

Background

The natriuretic peptides (NP) system has been considered an important regulator for ischemic stroke (IS) with a limited clinical implication. A better understanding of the underlying molecular mechanisms is urgent. Here, we aimed to examine the role of NP system genes methylation in IS.

Methods and Results

DNA methylation at promoter regions of four core NP system genes, e.g., CORIN, FURIN, NPPA, and NPPB, was measured by targeted bisulfite sequencing in 853 IS patients and 918 healthy controls. We first examined the association between DNA methylation at each single CpG and IS, followed by gene-based and gene-set analyses to examine the joint associations of DNA methylation at multiple CpGs in a gene or all four genes as a pathway with IS. After control of covariates and multiple testing, DNA methylation at 19 of the 36 assayed CpGs were individually associated with IS at q<0.05. The average methylation levels at the targeted regions of CORIN (OR=0.64, 95%CI: 0.5...