Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease.

Abstract

To evaluate DNA methylation sites and gene expression associated with coronary artery disease (CAD) and the possible pathological mechanism involved, we performed (1) genome-wide DNA methylation and mRNA expression profiling in peripheral blood datasets from the Gene Expression Omnibus repository of CAD samples and controls; (2) functional enrichment analysis and differential methylation gene regulatory network construction; (3) validation tests of 11 differential methylation positions of interest and the corresponding gene expression; and (4) correlation analysis for DNA methylation and mRNA expression data. A total of 669 differentially expressed mRNAs were matched to differentially methylated genes. After disease ontology, Kyoto Encyclopedia of Genes and Genomes pathway, gene ontology, protein-protein interaction and network construction and module analyses, 11 differentially methylated positions (DMPs) corresponding to 11 unique genes were observed: BDNF – cg26949694, BTRC - cg24381155, CDH5 - cg02223351, CXCL12 - cg11267527, EGFR - cg27637738, IL-6 - cg13104385, ITGB1 - cg20545410, PDGFRB - cg25613180, PIK3R1- cg00559992, PLCB1 - cg27178677 and PTPRC - cg09247619. After validation tests of 11 DMPs of interest and the corresponding gene expression, we found that CXCL12 was less hypomethylated in the CAD group, whereas the relative expression of ITGB1, PDGFRB and PIK3R1 was lower in CAD samples, and CXCL12 and ITGB1 methylation was negatively correlated with their expression. This study identified the correlation between DNA methylation and gene expression and highlighted the importance of CXCL12 in CAD pathogenesis.