Epigenetics regulation of HSD11B2 gene by promoter methylation in glucocorticoid-treated patients

Background: A diminished activity of hydroxysteroid (11-beta) dehydrogenase2 (11beta-HSD2) is regarded as a novel feature in the pathogenesis of hypertension by leading to an altered tetrahydrocortisol-versus tetrahydrocortisone-metabolites (THFs/THE) shuttle. Recent cell culture and animal studies suggest a role for promoter methylation, a major epigenetic feature of DNA, in regulation of HSD11B2 expression. However, little is known of human HSD11B2 epigenetic control and its relationship with the onset of hypertension. Objective: To evaluate the relevance of HSD11B2 promoter methylation in human peripheral blood mononuclear cells (PBMC) DNA, along with the urinary THFs/THE ratio, a biochemical indicator of 11beta-HSD2 activity, in blood pressure control. Methods: Twenty-five essential hypertensives and thirty-two subjects undergoing prednisone therapy were analyzed, the latter as a model for the understanding of 11beta-HSD2 function in the development of hypertension. Results: The elevated HSD11B2 methylation was associated to hypertension in glucocorticoid-treated patients and paralleled with the higher urinary THFs/THE ratio. Essential hypertensives with elevated urinary THFs/THE ratio also showed higher HSD11B2 promoter methylation. Conclusions: These results indicate a clinically relevant link between the epigenetic regulation through repression of HSD11B2 in PBMC DNA and the onset of hypertension.