Document Detail


Variation at the aldosterone synthase (CYP11B2) locus contributes to hypertension in subjects with a raised aldosterone-to-renin ratio.
MedLine Citation:
PMID:  12213905     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aldosterone-to-renin ratio (ARR) is a marker of aldosterone activity in hypertension. We examined the relationship of the ARR to the distribution of two biallelic polymorphisms at the CYP11B2 gene locus. One polymorphism affects a putative steroidogenic factor-1 binding site (-344 T/C) in the 5'-regulatory region, whereas the other marker reflects replacement of the intron-2 from CYP11B2 with that from the neighboring gene encoding 11beta-hydroxylase (CYP11B1; wild-type/conversion). We studied consecutive referrals to the Tayside hypertension clinic in 1998. Because the specificity of ARR (pmol/liter/ng/ml/h) for hyperaldosteronism increases with its threshold, ARRs of at least 750 and 1000 were used. A total of 375 patients were assessed; 86.9% had complete data. There were significant excesses of steroidogenic factor-1 (T) (ARR >/= 750, 0.62 vs. 0.51, P = 0.014; ARR >/= 1000, 0.63 vs. 0.51, P = 0.039) and intron-2 (conversion) (ARR >/= 750, 0.49 vs. 0.41, P = 0.205; ARR >/= 1000, 0.54 vs. 0.41, P = 0.029) alleles in patients with a raised ARR. The odds ratio for a raised ARR was 2.27 [95% confidence interval, 1.01, 5.09; P < 0.05] comparing patients with a homozygous haplotype for these alleles with those without any such alleles, and this risk increased with age. This study supports the notion that there is a genetic component that regulates aldosterone production and that hyperaldosteronism might develop over time in susceptible individuals.
Authors:
Pitt O Lim; Thomas M Macdonald; Christine Holloway; Elaine Friel; Niall H Anderson; Eleanor Dow; Roland T Jung; Eleanor Davies; Robert Fraser; John M C Connell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  87     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-05     Completed Date:  2002-10-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4398-402     Citation Subset:  AIM; IM    
Affiliation:
Hypertension Research Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom. limpo@cf.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Aldosterone / blood*
Aldosterone Synthase / genetics*
Base Sequence
Blood Pressure
Creatinine / blood
DNA Primers
Female
Genetic Variation*
Genotype
Humans
Hypertension / blood,  enzymology,  genetics*
Male
Middle Aged
Polymerase Chain Reaction
Potassium / blood
Renin / blood*
Sodium / blood
Chemical
Reg. No./Substance:
0/DNA Primers; 52-39-1/Aldosterone; 60-27-5/Creatinine; 7440-09-7/Potassium; 7440-23-5/Sodium; EC 1.14.15.4/Aldosterone Synthase; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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