title: 11β-Hydroxysteroid dehydrogenase type 2 in hypertension: comparison of phenotype and genotype analysis.
abstract: 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) catalyzes the inactivation of cortisol (F) to cortisone (E) in aldosterone target tissues, thereby protects mineralocorticoid receptor from F. Failure of 11β-HSD2 function is the basis of apparent mineralocorticoid excess, and its mild disturbances are suggested to lead to hypertension. The aim of the study was to analyze the 11β-HSD2 activity in hypertensives and healthy volunteers. Glucocorticoids (GCs) profile was estimated to verify whether the disorders of GCs balance may be involved in essential hypertension etiology. Exons and short introns of HSD11B2 were sequenced to evaluate existing mutations and their potential implications in the disease. The identified polymorphisms were assessed in case-control study to determine their relevance to hypertension. No significant differences in values of plasma F/E and UFF/UFE (urinary free F to free E) were observed between hypertensives and controls. The value of (THF+allo-THF)/(THE+allo-THE) (urinary tetrahydro-metabolites of F to tetrahydro-metabolites of E) in hypertensives was higher than in normotensives. Logistic regression demonstrated that the increase of one unit of (THF+allo-THF)/(THE+allo-THE) value increases the risk of hypertension over 11-fold. Genotyping indicated no hypertension related mutations in the coding region and short introns of HSD11B2.
authors.affiliation: Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznan, Poland. kasiakosicka@ump.edu.pl
authors.forename: K
authors.initials: K
authors.lastname: Kosicka
authors.forename: M
authors.initials: M
authors.lastname: Cymerys
authors.forename: A
authors.initials: A
authors.lastname: Majchrzak-Celińska
authors.forename: M
authors.initials: M
authors.lastname: Chuchracki
authors.forename: F K
authors.initials: FK
authors.lastname: Główka
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult
chemical_list: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2