European Heart Journal Advance Access published online on March 21, 2006
European Heart Journal, doi:10.1093/eurheartj/ehi833
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1 Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Rd, Bristol, BS8 2PR, UK
* To whom correspondence should be addressed. Aims One previous study among women with established coronary heart disease found a gene-treatment interaction between the oestrogen receptor gene (ESR1) and hormone replacement in their association with high density lipoprotein cholesterol (HDL-c). We aimed to replicate these findings in a general population sample. Methods and results Cross-sectional associations were assessed in a study of 3404 women from 23 towns across Britain who were aged 60-79 at the time of assessment and were described as white by the examining nurse. Women with the T-A haplotype [constructed from two single nucleotide polymorphisms (SNPs) in the first intron of ESR1: c454-397T>C (rs2234693) and c454-351A>G (rs9340799)], which was predicted to be associated with reduced oestrogen response, were more likely to have been past [per haplotype odds ratio 1.16 (95% CI 1.01, 1.33), P = 0.02] or to be current users [per haplotype odds ratio 1.19 (95% CI 0.99, 1.42), P = 0.05] of hormone replacement. However, there was no association between haplotype or either SNP and HDL-c or other cardiovascular disease risk factors and no statistical evidence of an interaction between hormone replacement use and haplotype or either SNP with respect to HDL-c or any other cardiovascular disease risk factors. Conclusion Women with the T-A haplotype are more likely to use hormone replacement. However, genotyping of ESR1 rs2234693 or rs9340799 in post-menopausal women to tailor hormone replacement is unlikely to markedly improve cardiovascular risk.
Received October 18, 2005
Revised February 12, 2006
Accepted February 23, 2006
Clinical research
The association of oestrogen receptor
Debbie A. Lawlor 1 *,
Nick Timpson 1,
Shah Ebrahim 2,
Ian NM Day 3,
and
George Davey Smith 1
-haplotypes with cardiovascular risk factors in the British Women's Heart and Health Study
2 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, UK
3 Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Rd, Bristol, BS8 2PR, UK; Human Genetics Division, School of Medicine, University of Southampton School of Medicine, UK
Debbie A. Lawlor, E-mail: d.a.lawlor{at}bristol.ac.uk
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