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

使用大型队列阐明遗传和生活方式因素之间的相互作用，以预防骨质疏松性骨折

基本信息

批准号：
18590579
负责人：
MORITA Akemi
金额：
$ 2.44万
依托单位：
National Institute of Health and Nutrition
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590579/
关键词：
Osteoporosis Fracture Polymorphism Tailor-maid Prevention Lifestyle Randomized Cohort Bone Mineral Density

项目摘要

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.

使用日本女性群体的大规模代表性样本，我们检查了几个候选基因中的单核苷酸多态性对骨矿物质密度（BMD）的影响，以及这些多态性和生活方式因素对 BMD 的相互作用。对于从日本 3 个市镇随机抽取的 1,651 名基线年龄为 15 至 79 岁的女性，我们在基线时使用 DXA 测量了腰椎、髋部和前臂远端的 BMD，并在基线后 3、6 和 10 年进行的随访研究中再次测量，作为 JPOS 队列研究的一部分。在队列中，有 133 名妇女在 10 年随访期间因死亡和搬家而退出。住处，1040完成了学业。通过对 720 名 50 岁及以上女性进行侧位胸片和椎体形态测定来诊断椎体骨折，并通过访谈评估临床骨折。 BMD 的变化根据受试者的年龄而变化。直到 45 岁时，每个骨骼部位的 BMD 才显示出任何显着变化。此后，每个部位的骨丢失均发生突然增加。通过PCR-RFLP方法和TaqMan等位基因区分测定法测定VDR、TGF-β、骨钙素、MTHFR、CYP19、CYP1A1、COMT、PPARγ、RUNX2、HSD17β和BMP2基因的多态性。在基线时，对 1,340 名女性进行了分析。每种基因型与基线 BMD 或任何骨骼部位随访前 3 年期间 BMD 的变化之间没有显着相关性。我们发现纳豆摄入量与绝经后女性股骨颈 BMD 的 CYP19 和 COMT 多态性之间存在显着的相互作用。此外，CYP19基因型之间骨质疏松症和骨质减少的患病率也不同。目前，我们正在研究这些候选基因与 10 年随访期间骨折事件之间的关联。