ABCA1, TCF7, NFATC1, PRKCZ and PDGFA DNA methylation as potential epigenetic-sensitive targets in acute coronary syndrome via network analysis

Acute coronary syndrome (ACS) is the most severe clinical manifestation of coronary heart disease.We performed an epigenome-wide analysis of circulating CD4 and CD8 T cells isolated from ACS patients and healthy subjects (HS), enrolled in the DIANA clinical trial, by reduced-representation bisulphite sequencing (RRBS). In CD4 T cells, we identified 61 differentially methylated regions (DMRs) associated with 57 annotated genes (53% hyper- and 47% hypo-methylated) by comparing ACS patients HS. In CD8 T cells, we identified 613 DMRs associated with 569 annotated genes (28% hyper- and 72% hypo-methylated) in ACS patients as compared to HS. In CD4 CD8 T cells of ACS patients we identified 175 statistically significant DMRs associated with 157 annotated genes (41% hyper- and 59% hypo-methylated). From pathway analyses, we selected six differentially methylated hub genes () and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients HS ( < 0.001). and gene expression was positively associated with CK-MB serum concentrations ( = 0.75, = 0.03; = 0.760, = 0.029; = 0.72, = 0.044; = 0.74, = 0.035, respectively).This pilot study is the first single-base resolution map of DNA methylome by RRBS in CD4 and CD8 T cells and provides specific methylation signatures to clarify the role of aberrant methylation in ACS pathogenesis, thus supporting future research for novel epigenetic-sensitive biomarkers in the prevention and early diagnosis of this pathology.