European Heart Journal Advance Access originally published online on March 21, 2006
European Heart Journal 2006 27(13):1597-1604; doi:10.1093/eurheartj/ehi833
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The association of oestrogen receptor 
-haplotypes with cardiovascular risk factors in the British Women's Heart and Health Study
1 Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Rd, Bristol, BS8 2PR, UK
2 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, UK
3 Human Genetics Division, School of Medicine, University of Southampton School of Medicine, UK
Received 18 October 2005; revised 12 February 2006; accepted 23 February 2006; online publish-ahead-of-print 21 March 2006.
* Corresponding author. Tel: +44 117 928 7267; fax: +44 117 928 7325. E-mail address: d.a.lawlor{at}bristol.ac.uk
See page 1519 for the editorial comment on this article (doi:10.1093/eurheartj/ehl065)
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.
Key Words: ESR1 • Oestrogen receptor • Hormone replacement • High density lipoprotein cholesterol
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