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Expression and gene variation studies deny association of human HSD3B1 gene with aldosterone production or blood pressure.
- Source :
-
American journal of hypertension [Am J Hypertens] 2015 Jan; Vol. 28 (1), pp. 113-20. Date of Electronic Publication: 2014 Jun 20. - Publication Year :
- 2015
-
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.<br />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).<br />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.<br />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.<br /> (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Aged
Cells, Cultured
Female
Gene Expression Regulation, Enzymologic
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Hypertension enzymology
Hypertension physiopathology
Male
Middle Aged
Netherlands
Phenotype
RNA, Messenger metabolism
Risk Factors
Adrenal Cortex enzymology
Aldosterone biosynthesis
Blood Pressure genetics
Hypertension genetics
Multienzyme Complexes genetics
Polymorphism, Single Nucleotide
Progesterone Reductase genetics
Steroid Isomerases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1941-7225
- Volume :
- 28
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 24951726
- Full Text :
- https://doi.org/10.1093/ajh/hpu103