相关实验视频
骨矿物质密度,骨质疏松症和骨质疏松性骨折:一个全基因组关联研究
J B Richards1, F Rivadeneira, M Inouye
1Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Lancet (London, England)
|May 6, 2008
概括
接近LRP5和TNFRSF11B的两个基因变异显著增加了骨质疏松症的风险. 这些常见的遗传因素有助于骨密度下降和骨折风险,这表明有可能对人口进行查.
科学领域:
- 遗传学 是一个遗传学.
- 骨生物学 骨生物学 骨生物学
- 骨质疏松症研究 骨质疏松症研究
背景情况:
- 骨质疏松症的诊断依赖于骨矿物密度 (BMD) 的测量.
- 骨质疏松症是一种复杂的特征,受遗传学和环境因素的影响.
- 确定BMD的遗传决定因素对于了解骨质疏松症病因至关重要.
研究的目的:
- 为了确定与骨矿物质密度 (BMD) 相关的遗传位置.
- 调查鉴定出的遗传变异与骨质疏松性骨折的关联.
主要方法:
- 在2,094名英国妇女中,对314,075个单核酸多态 (SNP) 的全基因组关联研究 (GWAS).
- 在三个欧洲队列中的6,463个个体中复制有前途的SNP.
- 在淋巴细胞细胞系中对基表达的分析.
- 用两个独立研究的数据对骨质疏松性骨折进行关联测试.
主要成果:
- 两个SNP,rs4355801 (接近TNFRSF11B) 和rs3736228 (在LRP5中),显示出全基因组显著的关联与BMD.
- LRP5 SNP (rs3736228) 与 BMD 降低和骨质疏松性骨折和骨质疏松症风险增加有关.
- 在TNFRSF11B (rs4355801) 附近的SNP与骨质量降低和骨质疏松症风险增加有关.
- 风险等位基因是常见的 (8557个人的22%),对骨和骨折风险有累积的影响.
- 对等位基表达的分析显示,rs4355801风险等位基携带者TNFRSF11B表达减少了一半.
结论:
- 在LRP5和TNFRSF11B中的遗传变异与骨质量下降和骨质疏松症和骨折风险增加有关.
- 这些共同风险基因对骨折风险的综合影响是显著的,与环境因素相比较.
- 这些风险等位基因的流行表明,在骨质疏松症查策略中可能发挥作用.
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