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A study in familial hypercholesterolemia suggests reduced methylomic plasticity in men with coronary artery disease

Simon-Pierre Guay1, Diane Brisson, Patrick Mathieu

  • 1Department of Biochemistry, Université de Sherbrooke, University-Affiliated Chicoutimi Hospital, 305 rue St-Vallier, Saguenay, Québec G7H 5H6, Canada.

Epigenomics
|February 18, 2015
PubMed

Insights

DNA methylation changes are linked to coronary artery disease (CAD) in men. Epigenome-wide analysis revealed differences in methylation patterns between men with and without CAD, suggesting a role for epigenetics in cardiovascular health.

Area of Science:

  • Epigenetics
  • Cardiovascular Disease Research
  • Molecular Biology

Background:

  • Coronary artery disease (CAD) is a leading cause of mortality worldwide.
  • Familial hypercholesterolemia (FH) is a genetic condition that increases CAD risk.
  • The role of DNA methylation in CAD pathogenesis remains incompletely understood.

Purpose of the Study:

  • To investigate the association between DNA methylation patterns and the presence of CAD.
  • To explore differences in DNA methylation between men with and without CAD, particularly within the FH population.

Main Methods:

  • Epigenome-wide analysis of DNA methylation in leukocytes from FH men with and without CAD.
  • Replication of key findings in larger cohorts of FH and non-FH men.
  • Statistical analysis to identify differentially methylated loci and their association with CAD and risk factors.

Main Results:

  • Men with CAD exhibited significantly more hypomethylated and hypermethylated loci compared to those without CAD.
  • Reduced DNA methylation level variability was observed in FH men with CAD.
  • Specific genes, COL14A1 and MMP9, showed DNA methylation levels associated with CAD, age of onset, and risk factors.

Conclusions:

  • Epigenome-wide DNA methylation alterations are associated with the occurrence of CAD in men.
  • These findings highlight the potential of epigenetic modifications as biomarkers or therapeutic targets for CAD.
  • Further research is warranted to elucidate the causal mechanisms linking DNA methylation to CAD development.
Abstract

Keywords:
DNA methylationarterial remodelingcandidate genescardiovascular diseasesepigenome-wide association studygene expressionmissing heritability

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