Relationship between Single Nucleotide Polymorphisms in CYP1A1 and CYP1B1 Genes and Bone Mineral Density in Postmenopausal Japanese Women on Hormone Replacement Therapy

Summary. The objective of this study was to evaluate the relationships between single nucleotide polymorphism of estrogen metabolizing genes and lumbar bone mineral density(BMD) and to determine the effects of hormone replacement therapy(HRT). We conducted a case study at the Niigata University Medical and Dental Hospital. The patients were 124 Japanese women diagnosed with osteopenia or osteoporosis and taking HRT for 12 months. Seven single nucleotide polymorphism(SNPs) in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) genes were characterized by a single nucleotide primer extension assay. The lumbar bone mineral density (BMD) were measured before and following 12 months of HRT. The genotyping of the 124 postmenopausal Japanese women revealed three out of seven SNPs to be quite common, with the minor allele frequency being at least 20％. A SNP in exon3 of CYP1B1 (L432V) was found to be significantly associated with the effect of HRT on BMD. In patients with the GG genotype of L432V, the responses to HRT in BMD markedly decreased. We demonstrated that a SNP in the CYP1B1 gene is associated with the magnitude of BMD in response to HRT. These results suggest that L432V polymorphism in the CYP1B1 gene could be used to predict the effect of HRT on lumbar BMD.