The association of oestrogen receptor alpha-haplotypes with cardiovascular risk factors in the British Women's Heart and Health Study.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Rd, Bristol, BS8 2PR, UK. d.a.lawlor@bristol.ac.uk
Debbie A
DA
Lawlor
Nick
N
Timpson
Shah
S
Ebrahim
Ian N M
IN
Day
George Davey
GD
Smith
D000368:Aged; D002318:Cardiovascular Diseases / Q000235:genetics*; D008076:Cholesterol, HDL / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005838:Genotype; D006239:Haplotypes; D020249:Hormone Replacement Therapy; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012923:Social Class; D049629:Waist-Hip Ratio
D008076:Cholesterol, HDL; D047628:Estrogen Receptor alpha; D005340:Fibrinogen