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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Publisher's URL: http://www.mdpi.com/1422-0067/18/3/579
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 > School of Cardiovascular & Metabolic Health 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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