Altered corticosteroid biosynthesis in essential hypertension: a digenic phenomenon

Davies, E., MacKenzie, S. M., Freel, E. M., Alvarez-Madrazo, S., Fraser, R. and Connell, J. M.C. (2009) Altered corticosteroid biosynthesis in essential hypertension: a digenic phenomenon. Molecular and Cellular Endocrinology, 300(1-2), pp. 185-191. (doi:10.1016/j.mce.2008.09.014)

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Publisher's URL: http://dx.doi.org/10.1016/j.mce.2008.09.014

Abstract

Aldosterone plays an important role in electrolyte and blood pressure homeostasis. Our studies have focused on the role of aldosterone in essential hypertension. We have shown that plasma aldosterone and ARR are heritable characteristics and that aldosterone concentrations in older subjects are inversely correlated with birthweight and positively correlated with blood pressure. Aldosterone levels are also associated with polymorphic variation in the CYP11B2 gene, which encodes aldosterone synthase, the enzyme responsible for aldosterone production. Interestingly, CYP11B2 polymorphisms are also associated with less efficient activity of 11β-hydroxylase, encoded by the neighbouring, highly homologous CYP11B1 gene. We propose that a digenic effect leads to increased aldosterone production, with inefficient 11β-hydroxylation causing a long-term increase in ACTH drive to the adrenal gland and enhanced expression of CYP11B2, thereby resulting in chronically raised aldosterone secretion in response to factors such as angiotensin II and potassium. In susceptible subjects this is likely, over many years, to result in hypertension with relative aldosterone excess.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilson-Davies, Dr Eleri and Connell, Professor John and Alvarez-Madrazo, Dr Samantha and Freel, Dr Marie and MacKenzie, Dr Scott and Fraser, Prof Robert
Authors: Davies, E., MacKenzie, S. M., Freel, E. M., Alvarez-Madrazo, S., Fraser, R., and Connell, J. M.C.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Molecular and Cellular Endocrinology
Publisher:Elsevier
ISSN:0303-7207
ISSN (Online):1872-8057
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences
392522Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences