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

• Published in: Epigenetics Vol. 17; no. 5; pp. 547 - 563
• Main Authors: Infante, Teresa, Franzese, Monica, Ruocco, Antonio, Schiano, Concetta, Affinito, Ornella, Pane, Katia, Memoli, Domenico, Rizzo, Francesca, Weisz, Alessandro, Bontempo, Paola, Grimaldi, Vincenzo, Berrino, Liberato, Soricelli, Andrea, Mauro, Ciro, Napoli, Claudio
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 04.05.2022; Taylor & Francis Group
• Subjects: Acute coronary syndrome; Acute Coronary Syndrome - genetics; ATP Binding Cassette Transporter 1 - genetics; ATP Binding Cassette Transporter 1 - metabolism; CD8-Positive T-Lymphocytes - metabolism; DNA Methylation; Epigenesis, Genetic; epigenetics; Humans; NFATC Transcription Factors - genetics; NFATC Transcription Factors - metabolism; Pilot Projects; Research Paper; T Cell Transcription Factor 1 - genetics; T Cell Transcription Factor 1 - metabolism; T lymphocytes; Transcription Factors - genetics; T lymphocytes; DNA methylation; Acute coronary syndrome; epigenetics
• ISSN: 1559-2294; 1559-2308; 1559-2308
• DOI: 10.1080/15592294.2021.1939481

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 vs 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 + vs 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 (NFATC1, TCF7, PDGFA, PRKCB, PRKCZ, ABCA1) and assessed their expression levels by q-RT-PCR. We found an up-regulation of selected genes in ACS patients vs HS (P < 0.001). ABCA1, TCF7, PDGFA, and PRKCZ gene expression was positively associated with CK-MB serum concentrations (r = 0.75, P = 0.03; r = 0.760, P = 0.029; r = 0.72, P = 0.044; r = 0.74, P = 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.