The large-scale gene analysis to develop the tailor-made prevention of osteoporosis

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Using a large-scale representative sample of the Japanese female population, we examined the effects of single nucleotide polymorphisms in the VDR, TGF-β, Osteocalcin, MTHFR, CYP19, CYP1A1 and COMT gene on bone mineral density (BMD), and the interactions between these polymorphisms and lifestyle factors on BMD. Fifty women were randomly selected from each of the 5-year age-stratified populations (15-79 years) in each of three chosen municipalities as a part of the Japanese population-based osteoporosis (JPOS) baseline study. BMD at the lumbar spine, hip and distal forearm were measured using DXA at baseline, and again in a follow-up study conducted three years after the baseline.Information on lifestyle factors was collected in a questionnaire and followed up in interviews. The polymorphisms were determined by the PCR-RFLP method and a TaqMan allelic discrimination assay. At baseline, 1,340 women were analyzed. There was no association between each genotype and the baseline BMD or the change in BMD at any of the skeletal sites. We found significant associations between daily milk consumption and baseline BMD at some skeletal sites, but only in subjects with GG genotype within a binding site of Cdx-2 in the VDR gene. There were significant positive associations between the natto intake and the rates of changes in BMD in postmenopausal women of JPOS study. We found significant interactions between the natto intake and CYP19 and COMT polymorphisms on BMD at femoral neck in postmenopausal women. In addition, the prevalence of osteoporosis and osteopenia was different between the genotypes of CYP19.In conclusion, each polymorphism alone did not have substantial effect on BMD in Japanese women. However, these polymorphisms might have some effect in women with specific lifestyle factors. Currently, we are studying the effects of other candidate genes on BMD and searching new polymorphisms associated with bone formation.