Document Detail


Epigenetic control of 11 beta-hydroxysteroid dehydrogenase 2 gene promoter is related to human hypertension.
MedLine Citation:
PMID:  18178212     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Simonetta Friso; Francesca Pizzolo; Sang-Woon Choi; Patrizia Guarini; Annalisa Castagna; Viviana Ravagnani; Antonio Carletto; Patrizia Pattini; Roberto Corrocher; Oliviero Olivieri
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-02-07
Journal Detail:
Title:  Atherosclerosis     Volume:  199     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-28     Completed Date:  2008-11-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  323-7     Citation Subset:  IM    
Affiliation:
Department of Clinical and Experimental Medicine, University of Verona School of Medicine, Verona, Italy. simonetta.friso@univr.it
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics*
Aged
DNA / metabolism
DNA Methylation
Epigenesis, Genetic*
Female
Glucocorticoids / metabolism
Humans
Hypertension / genetics*
Leukocytes, Mononuclear / cytology,  metabolism
Male
Middle Aged
Prednisone / therapeutic use
Promoter Regions, Genetic*
Transcription, Genetic
Chemical
Reg. No./Substance:
0/Glucocorticoids; 53-03-2/Prednisone; 9007-49-2/DNA; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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