Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy

PLoS One. 2016 Feb 12;11(2):e0148313. doi: 10.1371/journal.pone.0148313. eCollection 2016.

Abstract

Background: The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia.

Findings: We assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters.

Conclusion: The current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular System / metabolism
  • Cardiovascular System / physiopathology
  • CpG Islands*
  • DNA Methylation
  • Epigenesis, Genetic*
  • Female
  • Genetic Markers
  • Genome, Human*
  • Genome-Wide Association Study
  • Humans
  • Longitudinal Studies
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Risk Factors
  • Severity of Illness Index
  • Siblings
  • Time Factors
  • Twins, Monozygotic / genetics

Substances

  • Genetic Markers

Grants and funding

MvD is supported by the Netherlands Organisation for Scientific Research (NWO grant no 91611177). TN and PK are supported by the Dutch Program for Tissue Engineering (DPTE) and the Netherlands Initiative for Regenerative Medicine (NIRM). The funder (A-Skin) provided support in the form of salaries for authors [TN], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.