Is Any Cardiovascular Disease-Specific DNA Methylation Biomarker Within Reach?

Abstract

A detailed understanding of the epigenome of cardiovascular disease (CVD) should broaden current insights into mechanisms of atherogenesis and help identify suitable biomarkers for disease risk and progression. This review addresses the question whether a consensus has been reached on identifying the main aberrant DNA methylation profile in CVD. Additionally, it presents advances and setbacks in the search for specific CVD biomarkers. Although the literature points to DNA hypermethylation as an epigenetic landmark of CVD, inconsistencies are significant. In particular, the DNA methylomes of peripheral blood cells and the vascular wall do not show a consistent direction of change in all studies. An additional significant hurdle is the relatively low study-to-study reproducibility and the difficulty to assess specificity for CVD. Nonetheless, a number of biologically plausible markers have been proposed that warrant further studies. An integrated model for dynamic changes of DNA methylation during the natural history of atherosclerosis predisposition and progression is presented, that might reconcile conflicting findings. Cohort design and technical criteria for DNA methylation analysis need to be further homogenized to allow for meaningful validation. As stable DNA methylation profiles are likely determined by genetic variants, many of which might control a range of diseases, it is anticipated that CVD biomarker discovery will be a delicate balancing act between reproducibility and specificity.