Abstract
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-alpha (ERalpha) gene contribute to the effect of HRT on lumbar spine bone mineral density (BMD). Subjects were 84 post-menopausal women who had been taking HRT for 3 years to treat osteopenia or osteoporosis. Eighteen SNP in the ERalpha gene were characterized by a single nucleotide primer extension assay. Genotyping of the 84 individuals revealed that all SNP were quite common, the minor allele frequency being > or = 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). 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.
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