Association between single nucleotide polymorphisms of estrogen receptor alpha gene and efficacy of HRT on bone mineral density in post-menopausal Japanese women.
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-alpha (ERalpha) 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 ERalpha 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 > 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).


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.
Yahata
T
T
Department of Obstetrics & Gynecology, Niigata University School of Medicine, 1-757 Asahimachi-dori, Niigata 951-8510, Japan. yahatat@med.niigata-u.ac.jp
Quan
J
J
Tamura
N
N
Nagata
H
H
Kurabayashi
T
T
Tanaka
K
K
D000328:Adult; D000483:Alleles; D015519:Bone Density / Q000187:drug effects* / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D015914:Estrogen Replacement Therapy; D005260:Female; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008593:Menopause; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
D047628:Estrogen Receptor alpha