Association between DNA methylation and coronary heart disease or other atherosclerotic events: A systematic review

  • Alba Fernández-Sanlés
    Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Catalonia, Spain

    Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain
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  • Sergi Sayols-Baixeras
    Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Catalonia, Spain

    Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain

    CIBER Cardiovascular Diseases (CIBERCV), Barcelona, Catalonia, Spain
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  • Isaac Subirana
    Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Catalonia, Spain

    CIBER Epidemiology and Public Health (CIBERESP), Barcelona, Catalonia, Spain
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  • Irene R. Degano
    Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Catalonia, Spain

    CIBER Cardiovascular Diseases (CIBERCV), Barcelona, Catalonia, Spain
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  • Roberto Elosua
    Corresponding author. IMIM, Hospital del Mar Medical Research Institute, Dr Aiguader 88, 08003 Barcelona, Catalonia, Spain.
    Cardiovascular Epidemiology and Genetics Research Group, REGICOR Study Group, IMIM (Hospital Del Mar Medical Research Institute), Barcelona, Catalonia, Spain

    CIBER Cardiovascular Diseases (CIBERCV), Barcelona, Catalonia, Spain
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      • Global DNA methylation does not seem to be associated with CHD.
      • Candidate-gene studies proved four genes to be differentially methylated in CHD.
      • A set of 84 genes has been identified in at least two EWAS.
      • This set of genes could be prioritized in future analysis.
      • The EWAS results highlight the role of obesity, metabolism or inflammation in CHD.


      Background and aims

      The aim of this study was to perform a systematic review of the association between DNA methylation and coronary heart disease (CHD) or related atherosclerotic traits.


      A systematic review was designed. The condition of interest was DNA methylation, and the outcome was CHD or other atherosclerosis-related traits. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). A functional analysis was undertaken using the Ingenuity Pathway Analysis software.


      In total, 51 articles were included in the analysis: 12 global methylation, 34 candidate-gene and 11 EWAS, with six studies using more than one approach. The results of the global methylation studies were inconsistent. The candidate-gene results were consistent for some genes, suggesting that hypermethylation in ESRα, ABCG1 and FOXP3 and hypomethylation in IL-6 were associated with CHD. The EWAS identified 84 genes showing differential methylation associated with CHD in more than one study. The probability of these findings was <1.37·10−5. One third of these genes have been related to obesity in genome-wide association studies. The functional analysis identified several diseases and functions related to these set of genes: inflammatory, metabolic and cardiovascular disease.


      Global DNA methylation seems to be not associated with CHD. The evidence from candidate-gene studies was limited. The EWAS identified a set of 84 genes highlighting the relevance of obesity, inflammation, lipid and carbohydrate metabolism in CHD. This set of genes could be prioritized in future studies assessing the role of DNA methylation in CHD.

      Graphical abstract


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