Genetic biomarkers of hypertension and future challenges integrating epigenomics

Essential hypertension is a multifactorial disease, considered to be one of the world's greatest public health problems. Despite recent, major, technical advances aiming to elucidate its genetic component, the discovered biomarkers up to now were reported to have only small effects, explaining consequently a tiny fraction of its phenotypic variance and resulting in a large proportion of missing heritability. Likewise, little evidence is available with regard to the epigenetic regulation of essential hypertension, since no robust biomarkers have yet been reported. In the current review, we discuss the main approaches used exclusively to study the genetics and epigenetics of essential hypertension, the biomarkers identified, their clinical utility and the difficulties to be overcome. Furthermore, we propose a new category of functional genetic-epigenetic biomarkers, eMethSNPs, and we provide their hypothetical gene expression profiles for a genetic functional regulation of hypertension via DNA methylation. Though believed to be infrequent, eMethSNPs could constitute a new category of mechanistically-based genetic biomarkers predisposing to essential hypertension.