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

Authors
  • Infante, Teresa1
  • Franzese, Monica2
  • Ruocco, Antonio3
  • Schiano, Concetta1
  • Affinito, Ornella2
  • Pane, Katia2
  • Memoli, Domenico4, 5
  • Rizzo, Francesca4, 5
  • Weisz, Alessandro4, 5
  • Bontempo, Paola6
  • Grimaldi, Vincenzo2, 7
  • Berrino, Liberato8
  • Soricelli, Andrea2, 9
  • Mauro, Ciro3
  • Napoli, Claudio1, 2
  • 1 Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", Naples, Italy. , (Italy)
  • 2 IRCCS SDN, Naples, Italy. , (Italy)
  • 3 Unit of Cardiovascular Diseases and Arrhythmias, "Antonio Cardarelli" Hospital, Naples, Italy. , (Italy)
  • 4 Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana," University of Salerno, Baronissi, SA, Italy. , (Italy)
  • 5 Genome Research Center for Health, Campus of Medicine, Baronissi, SA, Italy. , (Italy)
  • 6 Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. , (Italy)
  • 7 U.O.C. Division of Clinical Immunology, Immunohematology, Transfusion Medicine and Transplant Immunology, University of Campania "Luigi Vanvitelli", Naples, Italy. , (Italy)
  • 8 Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. , (Italy)
  • 9 Department of Exercise and Wellness Sciences, University of Naples Parthenope, Naples, Italy. , (Italy)
Type
Published Article
Journal
Epigenetics
Publisher
Landes Bioscience
Publication Date
May 01, 2022
Volume
17
Issue
5
Pages
547–563
Identifiers
DOI: 10.1080/15592294.2021.1939481
PMID: 34151742
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

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