title: Epigenetic control of 11 beta-hydroxysteroid dehydrogenase 2 gene promoter is related to human hypertension.
abstract: BACKGROUND
  Lower activity of 11 beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) classically induces 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. Little is known, however, of human HSD11B2 epigenetic control and its relationship with the onset of hypertension.
  
  
  OBJECTIVE
  To explore the possible relevance of HSD11B2 promoter methylation, by examining human peripheral blood mononuclear cell (PBMC) DNA and urinary THFs/THE ratio as a biochemical indicator of 11beta-HSD2 activity, in blood pressure control.
  
  
  METHODS
  Twenty-five essential hypertensives and 32 subjects on prednisone therapy were analyzed, the latter to investigate 11beta-HSD2 function in the development of hypertension.
  
  
  RESULTS
  Elevated HSD11B2 promoter methylation was associated with hypertension developing in glucocorticoid-treated patients in parallel with a higher urinary THFs/THE ratio. Essential hypertensives with elevated urinary THFs/THE ratio also showed higher HSD11B2 promoter methylation.
  
  
  CONCLUSIONS
  These results show a clear link between the epigenetic regulation through repression of HSD11B2 in PBMC DNA and hypertension.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Verona School of Medicine, Verona, Italy. simonetta.friso@univr.it
authors.forename: Simonetta
authors.initials: S
authors.lastname: Friso
authors.forename: Francesca
authors.initials: F
authors.lastname: Pizzolo
authors.forename: Sang-Woon
authors.initials: SW
authors.lastname: Choi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Guarini
authors.forename: Annalisa
authors.initials: A
authors.lastname: Castagna
authors.forename: Viviana
authors.initials: V
authors.lastname: Ravagnani
authors.forename: Antonio
authors.initials: A
authors.lastname: Carletto
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pattini
authors.forename: Roberto
authors.initials: R
authors.lastname: Corrocher
authors.forename: Oliviero
authors.initials: O
authors.lastname: Olivieri
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics*; D000368:Aged; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D005938:Glucocorticoids; D004247:DNA; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D011241:Prednisone