| Budget Amount *help |
¥3,810,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
Using a large-scale representative sample of the Japanese female population, we examined the effects of single nucleotide polymorphisms in several candidate genes on bone mineral density (BMD), and the interactions between these polymorphisms and lifestyle factors on BMD. For 1,651 women aged 15 to 79 years at baseline selected randomly from 3 municipalities in Japan, we measured BMD at the lumbar spine, hip and distal forearm using DXA at baseline, and again in a follow-up study conducted 3, 6 and 10 years after the baseline as a part of JPOS Cohort Study.
Among the cohort from which 133 women dropped out during the 10-year follow-up because of deaths and move of residence, 1040 completed the study. Vertebral fractures were diagnosed using lateral chest radiographs with vertebral morphometry in 720 women aged 50 and over Clinical fractures were assessed by the interview. The changes in BMD varied according to ages of subjects. BMD did not show any significant change until 45 years at every skeletal site. After that, an abrupt increase in bone loss occurred at each site.
The polymorphisms in the VDR, TGF-beta, Osteocalcin, MTHFR, CYP19, CYP1A1, COMT, PPARγ, RUNX2, HSD17beta and BMP2 gene were determined by the PCR-RFLP method and a TaqMan allelic discrimination assay. At baseline, 1,340 women were analyzed. There were no significant associations between each genotype and the baseline BMD or the change in BMD during the first 3 years of follow-up at any of the skeletal sites. 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. Currently, we are studying the association between these candidate genes and incident fractures during 10 years follow-up.
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