title: Expression and gene variation studies deny association of human HSD3B1 gene with aldosterone production or blood pressure.
abstract: BACKGROUND
  Recent evidence suggests that the type I 3β-hydroxysteroid dehydrogenase, a steroidogenic enzyme encoded by the HSD3B1 gene, could be involved in aldosterone production and that genetic variation in HSD3B1 is associated with blood pressure. These findings challenge the long-standing hypothesis that all adrenocortical steroidogenesis is executed by the type II iso-enzyme, encoded by HSD3B2.
  
  
  METHODS
  To verify these findings, the adrenal presence of HSD3B1 and its effect on aldosterone synthesis and blood pressure were studied in expression and genetic association analyses, respectively. Expression of HSD3B1 and HSD3B2 was investigated in various adrenocortical tissues (n = 15) and in primary adrenal cell cultures (n = 5) after stimulation with adrenocorticotropin and angiotensin II. Six tagging single nucleotide polymorphisms within the HSD3B1 gene were studied for association with blood pressure and hypertension in a meta-analysis of 4 Dutch cohorts (n = 11,192).
  
  
  RESULTS
  HSD3B1 expression was minimal or absent in adrenocortical tissues, including 6 aldosterone-producing adenomas. In contrast with the ubiquitously expressed HSD3B2 mRNA, HSD3B1 levels were not stimulated by adrenocorticotropin or angiotensin II. No variants in the HSD3B1 gene were associated with blood pressure or the occurrence of hypertension.
  
  
  CONCLUSIONS
  We found no evidence to support confirmation that HSD3B1 is involved in aldosterone synthesis in the human adrenal cortex or that genetic variation in HSD3B1 affects blood pressure or hypertension, favoring the hypothesis that all adrenocortical steroidogenesis is primarily dependent on the type II 3β-hydroxysteroid dehydrogenase.
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Germaine C
authors.initials: GC
authors.lastname: Verwoert
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hofland
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;
authors.forename: Najaf
authors.initials: N
authors.lastname: Amin
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Francesco U S
authors.initials: FU
authors.lastname: Mattace-Raso
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.affiliation: Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. a.danser@erasmusmc.nl.
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
mesh_terms: D000302:Adrenal Cortex / Q000201:enzymology*; D000368:Aged; D000450:Aldosterone / Q000096:biosynthesis*; D001794:Blood Pressure / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics*; D009426:Netherlands; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011375:Progesterone Reductase / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D013251:Steroid Isomerases / Q000235:genetics*
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D000450:Aldosterone; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; D013251:Steroid Isomerases
keywords: HSD3B1; aldosterone; blood pressure; hypertension.