Document Detail

Novel estrogen receptor alpha promoter polymorphism increases ventricular hypertrophic response to hypertension.
MedLine Citation:
PMID:  17095210     Owner:  NLM     Status:  MEDLINE    
Given the strong genetic contribution to blood pressure and left ventricular hypertrophy (LVH), and the influence of estrogen on these parameters, we hypothesized that polymorphisms in the estrogen receptor alpha (ERalpha) promoter may influence LVH. Three novel polymorphisms were identified upstream of the ERalpha alternatively spliced exon 1E, within sequence which demonstrated significant promoter activity in vitro. Demonstration of ERalpha E isoform expression in human ventricle by RT-PCR supported a possible functional role for the 1E novel polymorphisms in estrogen signaling in the heart. Indeed, G>A (-721 E) was significantly associated with LVH after controlling for systolic blood pressure and sex in a healthy population (n=74), contributing to 23% of interventricular septum (IVS) width variance (p<0.001) and 9.4% of left ventricular mass index (LVMI) variance (p=0.035). In a separate hypertensive cohort, male carriers of the A allele (n=8) had a 17% increase in IVS (95% CI: 6-28%) and a 19% increase in LVMI (3-34%) compared to GG homozygotes (n=84). We conclude that a novel polymorphism in the promoter of a cardiac mRNA splice isoform of ERalpha is associated with LVH.
G A Figtree; A Kindmark; L Lind; E Grundberg; B Speller; B G Robinson; K M Channon; H Watkins
Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't     Date:  2006-11-13
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  103     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-29     Completed Date:  2007-03-15     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  110-8     Citation Subset:  IM    
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
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MeSH Terms
Alternative Splicing
Cohort Studies
DNA Mutational Analysis
Estrogen Receptor alpha / genetics*
Genetic Testing
Hypertension / complications,  genetics*
Hypertrophy, Left Ventricular / etiology,  genetics*
Middle Aged
Polymorphism, Genetic*
Promoter Regions, Genetic*
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Estrogen Receptor alpha

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