DNA methylation and cardiovascular disease in humans: a systematic review and database of known CpG methylation sites

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Abstract
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Cardiovascular disease (CVD) is the leading cause of death worldwide and considered one of the most environmentally driven diseases. The role of DNA methylation in response to the individual exposure for the development and progression of CVD is still poorly understood and a synthesis of the evidence is lacking.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>A systematic review of articles examining measurements of DNA cytosine methylation in CVD was conducted in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The search yielded 5,563 articles from PubMed and CENTRAL databases. From 99 studies with a total of 87,827 individuals eligible for analysis, a database was created combining all CpG-, gene- and study-related information. It contains 74,580 unique CpG sites, of which 1452 CpG sites were mentioned in ≥ 2, and 441 CpG sites in ≥ 3 publications. Two sites were referenced in ≥ 6 publications: cg01656216 (near <jats:italic>ZNF438</jats:italic>) related to vascular disease and epigenetic age, and cg03636183 (near <jats:italic>F2RL3</jats:italic>) related to coronary heart disease, myocardial infarction, smoking and air pollution. Of 19,127 mapped genes, 5,807 were reported in ≥ 2 studies. Most frequently reported were <jats:italic>TEAD1</jats:italic> (TEA Domain Transcription Factor 1) and <jats:italic>PTPRN2</jats:italic> (Protein Tyrosine Phosphatase Receptor Type N2) in association with outcomes ranging from vascular to cardiac disease. Gene set enrichment analysis of 4,532 overlapping genes revealed enrichment for Gene Ontology molecular function “DNA-binding transcription activator activity” (<jats:italic>q</jats:italic> = 1.65 × 10<jats:sup>–11</jats:sup>) and biological processes “skeletal system development” (<jats:italic>q</jats:italic> = 1.89 × 10<jats:sup>–23</jats:sup>). Gene enrichment demonstrated that general CVD-related terms are shared, while “heart” and “vasculature” specific genes have more disease-specific terms as PR interval for “heart” or platelet distribution width for “vasculature.” STRING analysis revealed significant protein–protein interactions between the products of the differentially methylated genes (<jats:italic>p</jats:italic> = 0.003) suggesting that dysregulation of the protein interaction network could contribute to CVD. Overlaps with curated gene sets from the Molecular Signatures Database showed enrichment of genes in hemostasis (<jats:italic>p</jats:italic> = 2.9 × 10<jats:sup>–6</jats:sup>) and atherosclerosis (<jats:italic>p</jats:italic> = 4.9 × 10<jats:sup>–4</jats:sup>).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>This review highlights the current state of knowledge on significant relationship between DNA methylation and CVD in humans. An open-access database has been compiled of reported CpG methylation sites, genes and pathways that may play an important role in this relationship.</jats:p> </jats:sec>
Autoren
  • Mykhailo Krolevets
  • Vincent ten Cate
  • Jürgen H Prochaska
  • Andreas Schulz
  • Steffen Rapp
  • Stefan Tenzer
  • Miguel A Andrade-Navarro
  • Steve Horvath
  • Christof Niehrs
  • Philipp S Wild
DOI
10.1186/s13148-023-01468-y
eISSN
1868-7083
Ausgabe der Veröffentlichung
1
Zeitschrift
Clinical Epigenetics
Sprache
en
Artikelnummer
56
Online publication date
2023
Status
Published online
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1186/s13148-023-01468-y
Datum der Datenerfassung
2023
Titel
DNA methylation and cardiovascular disease in humans: a systematic review and database of known CpG methylation sites
Ausgabe der Zeitschrift
15

Datenquelle: Crossref

Andere Metadatenquellen:
Author's licence
CC-BY
Autoren
  • Mykhailo Krovelets
  • Vincent ten Cate
  • Jürgen H Prochaska
  • Andreas Schulz
  • Steffen Rapp
  • Stefan Tenzer
  • Miguel A Andrade-Navarro
  • Steve Horvath
  • Christof Niehrs
  • Philipp S Wild
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-491381577-G
Resource version
Published version
DOI
10.1186/s13148-023-01468-y
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft (DFG)|491381577|Open-Access-Publikationskosten 2022–2024 Universität Mainz - Universitätsmedizin
File(s) embargoed
false
Open access
true
ISSN
1868-7083
Zeitschrift
Clinical epigenetics
Schlüsselwörter
  • 610 Medizin
  • 610 Medical sciences
Sprache
eng
Open access status
Open Access
Paginierung
56
Datum der Veröffentlichung
2023
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/9435
Herausgeber
Springer
Datum der Datenerfassung
2023
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Zugang
Public
Titel
DNA methylation and cardiovascular disease in humans : a systematic review and database of known CpG methylation sites
Ausgabe der Zeitschrift
15

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dna_methylation_and_cardiovas-20230816121309050.pdf

Datenquelle: OPENSCIENCE.UB

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