ACTH and polymorphisms at steroidogenic loci as determinants of aldosterone secretion and blood pressure

MacKenzie, S. M. , Freel, M., Connell, J. M., Fraser, R. and Davies, E. (2017) ACTH and polymorphisms at steroidogenic loci as determinants of aldosterone secretion and blood pressure. International Journal of Molecular Sciences, 18(3), 579. (doi:10.3390/ijms18030579) (PMID:28272372) (PMCID:PMC5372595)

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Abstract

The majority of genes contributing to the heritable component of blood pressure remain unidentified, but there is substantial evidence to suggest that common polymorphisms at loci involved in the biosynthesis of the corticosteroids aldosterone and cortisol are important. This view is supported by data from genome-wide association studies that consistently link the CYP17A1 locus to blood pressure. In this review article, we describe common polymorphisms at three steroidogenic loci (CYP11B2, CYP11B1 and CYP17A1) that alter gene transcription efficiency and levels of key steroids, including aldosterone. However, the mechanism by which this occurs remains unclear. While the renin angiotensin system is rightly regarded as the major driver of aldosterone secretion, there is increasing evidence that the contribution of corticotropin (ACTH) is also significant. In light of this, we propose that the differential response of variant CYP11B2, CYP11B1 and CYP17A1 genes to ACTH is an important determinant of blood pressure, tending to predispose individuals with an unfavourable genotype to hypertension.

Item Type:Articles
Additional Information:Special Issue: Selected Papers from the Renin–Angiotensin–Aldosterone System (RAAS)2016: Official Satellite of ISH2016, from September 23 to 24 in Tokyo, Japan
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Davies, Professor Eleanor and Connell, Professor John and Freel, Dr Marie and MacKenzie, Dr Scott
Authors: MacKenzie, S. M., Freel, M., Connell, J. M., Fraser, R., and Davies, E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:International Journal of Molecular Sciences
Publisher:MDPI
ISSN:1661-6596
ISSN (Online):1422-0067
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in International Journal of Molecular Sciences 18(3):579
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
646581Understanding the genetic regulation of adrenal steroid hormones in cardiovascular disease �\200\223 Developing a stratified approach to cardiovascular careEleanor DaviesScottish Executive Health Department (SEHHD-CSO)ETM/326RI CARDIOVASCULAR & MEDICAL SCIENCES
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874/71954RI CARDIOVASCULAR & MEDICAL SCIENCES
496251Translational studies on the role of corticosteroids in cardiovascular diseaseMarie FreelMedical Research Council (MRC)G0802803RI CARDIOVASCULAR & MEDICAL SCIENCES