Hum. Reprod. Advance Access originally published online on April 14, 2005
Human Reproduction 2005 20(7):1860-1866; doi:10.1093/humrep/deh895
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Association between single nucleotide polymorphisms of estrogen receptor 
gene and efficacy of HRT on bone mineral density in post-menopausal Japanese women
Department of Obstetrics & Gynecology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Niigata 951-8510, Japan
1 To whom correspondence should be addressed. Email: yahatat{at}med.niigata-u.ac.jp
BACKGROUND: Although HRT for post-menopausal women can protect against bone loss, variations in bone responses exist. We studied whether single nucleotide polymorphisms (SNP) of the estrogen receptor-
(ER) gene contribute to the effect of HRT on lumbar spine bone mineral density (BMD). METHODS: Subjects were 84 post-menopausal women who had been taking HRT for 3 years to treat osteopenia or osteoporosis. Eighteen SNP in the ER gene were characterized by a single nucleotide primer extension assay. RESULTS: Genotyping of the 84 individuals revealed that all SNP were quite common, the minor allele frequency being 
20%. A SNP in intron 6 (IVS6+14144) was significantly associated with the response to HRT for the first 3 years after starting treatment (P=0.043, 0.025 and 0.032 for the first, second and third years respectively). Haplotype analysis revealed that a combination of SNP IVS6+14144 and IVS4+4238 was significantly correlated with the response to HRT; women with haplotype G–G (IVS6 14144–IVS4 4238) showed a significantly higher response (P=0.014, 0.043 and 0.010 for the first second and third year respectively). CONCLUSIONS: These results suggest that a specific SNP and the haplotype of the selected SNP could be used to predict the effect of HRT on lumbar BMD.
Key words:
bone mineral density/estrogen receptor /haplotype/hormone replacement therapy/single nucleotide polymorphism
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