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Int. J. Mol. Sci. 2017, 18(3), 579; doi:10.3390/ijms18030579

ACTH and Polymorphisms at Steroidogenic Loci as Determinants of Aldosterone Secretion and Blood Pressure

1
Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK
2
Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Anastasia Susie Mihailidou, Jan Danser, Sadayoshi Ito, Fumitoshi Satoh and Akira Nishiyama
Received: 10 February 2017 / Revised: 28 February 2017 / Accepted: 2 March 2017 / Published: 7 March 2017
View Full-Text   |   Download PDF [220 KB, uploaded 8 March 2017]

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. View Full-Text
Keywords: hypertension; ACTH; aldosterone; CYP11B2; CYP11B1; CYP17A1 hypertension; ACTH; aldosterone; CYP11B2; CYP11B1; CYP17A1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

MacKenzie, S.M.; Freel, E.M.; Connell, J.M.; Fraser, R.; Davies, E. ACTH and Polymorphisms at Steroidogenic Loci as Determinants of Aldosterone Secretion and Blood Pressure. Int. J. Mol. Sci. 2017, 18, 579.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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