Novel methylation mark and essential hypertension.

Abstract

Background: Essential hypertension (EH) is an important risk factor for various cardiovascular, cerebral and renal disorders. It is a multi-factorial trait which occurs through complex interplay between genetic, epigenetic, and environmental factors. Even after advancement of technology and deciphering the involvement of multiple signalling pathways in blood pressure regulation, it still remains as a huge global concern. Genome-wide association studies (GWAS) have revealed EH-associated genetic variants but these solely cannot explain the variability in blood pressure indicating the involvement of additional factors. The etiopathogenesis of hypertension has now advanced to the level of epigenomics where aberrant DNA methylation is the most defined epigenetic mechanism to be involved in gene regulation. Though role of DNA methylation in cancer and other mechanisms is deeply studied but this mechanism is in infancy in relation to hypertension. Generally, 5-methylcytosine (5mC) levels are being targeted at both individual gene and global level to find association with the disease. But recently, with advanced sequencing techniques another methylation mark, N6-methyladenine (6mA) was found and studied in humans which was earlier considered to be absent in case of eukaryotes. Relation of aberrant 6mA levels with cancer and stem cell fate has drawn attention to target 6mA levels with hypertension too.

Conclusion: Recent studies targeting hypertension has suggested 6mA levels as novel marker and its demethylase, ALKBH1 as probable therapeutic target to prevent hypertension through epigenetic programming. This review compiles different methylation studies and suggests targeting of both 5mC and 6mA levels to cover role of methylation in hypertension in broader scenario.