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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Association between aldosterone production and variation in the 11β-hydroxylase (CYP11B1) gene
Journal of Clinical Endocrinology and Metabolism, Volume 91, No. 12, Year 2006
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Description
Context: Variation in the region of chromosome 8 including the genes steroid 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) influences mineralocorticoid and glucocorticoid metabolism. However, the relative importance of polymorphisms in CYP11B1 and CYP11B2 in determining these phenotypes is unknown. Objective: Our objective was to investigate genetic influences of the CYP11B1 and CYP11B2 genes on mineralocorticoid metabolism. Design: We measured 24-h urinary excretion of the key metabolites of the principal mineralocorticoids, glucocorticoids and androgens secreted by the adrenal cortex. We genotyped polymorphisms spanning the CYP11B1 and CYP11B2 genes, which together capture all common variations at the locus. Participants: Participants included 573 members of 105 British Caucasian families ascertained on a hypertensive proband. Main Outcome Measures: We assessed heritability of urinary tetrahydroaldosterone (THAldo) excretion and association of THAldo excretion with genotype. Results: The heritability of THAldo excretion was 52% (P < 10-6). There was significant association between THAldo and genotype at several of the CYP11B1/B2 polymorphisms. The strongest association was observed at the rs6387 (2803A/G) polymorphism in intron 3 of CYP11B1 (P = 0.0004). Association followed a codominant model with a 21% higher THAldo excretion per G allele. Genotype at rs6387 accounted for 2.1% of the total population variability of THAldo. We found significant association between THAldo excretion and urinary total androgen excretion, urinary tetrahydrodeoxycortisol level, and urinary cortisol metabolites (all P < 0.001). Conclusions: Aldosterone synthesis is highly heritable and is affected by genotype at CYP11B1. Our findings support the hypothesis that genetically determined differences in 11-hydroxylation efficiency can have downstream effects on mineralocorticoid synthesis. Such effects may be of relevance to the development of low-renin essential hypertension. Copyright © 2006 by The Endocrine Society.
Authors & Co-Authors
Imrie, Helen
United Kingdom, Newcastle
Newcastle University
Freel, Marie
United Kingdom, Glasgow
University of Glasgow
Mayosi, Bongani M.
South Africa, Cape Town
University of Cape Town
Davies, Eleanor
United Kingdom, Glasgow
University of Glasgow
Fräser, Robert B.
United Kingdom, Glasgow
University of Glasgow
Ingram, Mary C.
United Kingdom, Glasgow
University of Glasgow
Cordell, Heather Jane
United Kingdom, Newcastle
Newcastle University
Farrall, Martin
United Kingdom, Oxford
University of Oxford
Avery, Peter J.
United Kingdom, Newcastle
Newcastle University
Watkins, Hugh C.
United Kingdom, Oxford
University of Oxford
Keavney, Bernard D.
United Kingdom, Newcastle
Newcastle University
United Kingdom, Newcastle
University of Newcastle Upon Tyne, Faculty of Medical Sciences
Connell, John M.C.
United Kingdom, Glasgow
University of Glasgow
Statistics
Citations: 12
Authors: 12
Affiliations: 5
Identifiers
Doi:
10.1210/jc.2006-1481
ISSN:
0021972X
e-ISSN:
0021972X
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cross Sectional Study