Clarification of the interaction between genetic and lifestyle factors for the railor-made prevention of osteoporotic fracture using a large cohort

利用日本女性人口的大规模代表性样本，我们研究了几个候选基因的单核苷酸多态性对骨密度（BMD）的影响，以及这些多态性与生活方式因素之间的相互作用。从日本3个城市随机选择1651名年龄在15至79岁之间的女性，我们在基线时使用DXA测量腰椎、髋关节和前臂远端的骨密度，并在基线后进行3年、6年和10年的随访研究，作为JPOS队列研究的一部分。在这一队列中，133名妇女在10年随访期间因死亡和搬家而退出，其中1040人完成了研究。720名50岁及以上的女性采用椎体形态测量的侧位胸片诊断椎体骨折。骨密度的变化随受试者年龄的不同而不同。直到45岁，骨密度才在每个骨骼部位显示出任何显著的变化。在那之后，每个部位的骨质流失突然增加。采用PCR-RFLP法和TaqMan等位基因鉴别法检测VDR、tgf - β、骨钙素、MTHFR、CYP19、CYP1A1、COMT、PPARγ、RUNX2、hsd17 β和BMP2基因多态性。在基线时，分析了1340名妇女。每种基因型与基线骨密度或骨密度在任何骨骼部位的前3年随访期间的变化之间没有显著关联。我们发现纳豆摄入量与绝经后妇女股骨颈骨密度的CYP19和COMT多态性之间存在显著的相互作用。此外，不同基因型CYP19的骨质疏松和骨质减少的患病率也不同。目前，我们正在10年随访期间研究这些候选基因与意外骨折之间的关系。

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.