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

大规模基因分析开发量身定制的骨质疏松预防方案

基本信息

批准号：
16590522
负责人：
MORITA Akemi
金额：
$ 2.3万
依托单位：
Kinki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

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.

利用日本女性人群的大规模代表性样本，我们研究了VDR、TGF-β、骨钙素、MTHFR、CYP19、CYP1A1和COMT基因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。作为日本基于人口的骨质疏松症（JPOS）基线研究的一部分，研究人员从三个选定的城市的5岁年龄分层人群（15-79岁）中随机抽取50名妇女。在基线时使用DXA测量腰椎、髋关节和前臂远端的骨密度，并在基线后进行三年的随访研究。有关生活方式因素的信息以问卷形式收集，并在访谈中进行跟踪。采用PCR-RFLP法和TaqMan等位基因鉴别法测定多态性。在基线时，分析了1340名妇女。每种基因型与基线骨密度或任何骨骼部位骨密度变化之间没有关联。我们发现每日牛奶摄入量与某些骨骼部位的基线骨密度之间存在显著关联，但仅适用于VDR基因中Cdx-2结合位点内GG基因型的受试者。在JPOS研究中，纳豆摄入量与绝经后妇女骨密度变化率之间存在显著的正相关。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。总之，每种多态性单独对日本女性的骨密度没有实质性影响。然而，这些多态性可能对具有特定生活方式因素的女性有一定影响。目前，我们正在研究其他候选基因对骨密度的影响，并寻找与骨形成相关的新多态性。