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

利用日本女性群体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对骨密度的影响，以及这些多态与生活方式因素对骨密度的影响。我们从日本3个城市随机选择了1651名年龄在15岁到79岁之间的基线女性，使用DXA测量了基线时腰椎、髋部和前臂远端的骨密度，并在基线后3、6和10年进行了随访研究，作为JPOS队列研究的一部分。在133名女性因死亡和迁居而在10年的随访中退出的队列中，1040人完成了研究。720名50岁及以上女性的侧位胸片结合椎体形态测量诊断椎体骨折通过访谈评估临床骨折。骨密度的变化随年龄的变化而不同。每个骨骼部位的骨密度直到45年才有明显变化。采用聚合酶链式反应-限制性片段长度多态性方法和TaqMan等位基因鉴别分析方法检测维生素D受体、转化生长因子-β、骨钙素、亚甲基四氢叶酸还原酶、细胞色素PYP19、细胞色素PYP1A1、骨钙素等位基因的多态性。在基线时，对1340名女性进行了分析。在任何骨骼部位的前3年的随访中，每种基因型与基线骨密度或骨密度变化之间没有显著的相关性。我们发现，在绝经后妇女中，纳豆摄入量与股骨颈骨密度的CYP19和COMT基因多态之间存在显著的交互作用。此外，骨质疏松症和骨量减少的患病率在不同的CYP19基因型之间也不同。目前，我们正在研究这些候选基因与10年随访中发生的骨折之间的关系。

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.