Department of Molecular Psychiatry, Life and Brain Center, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
Hum Genet. 2009 Nov;126(5):629-36. doi: 10.1007/s00439-009-0708-8. Epub 2009 Jun 30.
Genetic variants within the CNR2 gene encoding the cannabinoid receptor CB2 have been shown to be associated with osteoporosis and low bone mineral density (BMD) in case-control studies. We now examined the association of polymorphisms in CNR2 with hand bone strength in an ethnically homogeneous healthy family sample of European origin (Chuvashians) living in Russia. We show that non-synonymous CNR2 SNPs are significantly associated with radiographic hand BMD and breaking bending resistance index (BBRI) by two different transmission disequilibrium tests. For both tests highly significant p values (ranging from 0.007 to 0.008 for hand BMD, and from 0.001 to 0.003 for BBRI) were also obtained with additional SNPs at the CNR2 locus. The associations remained significant after correction for multiple testing. In conclusion, in addition to the association of CNR2 polymorphisms with low BMD at selected clinically relevant skeletal sites, we now report their significant association with hand bone strength phenotypes using a family-based study design implying an even broader impact of genetic variation at the CNR2 locus on bone structure and function.
研究表明，编码大麻素受体 CB2 的 CNR2 基因内的遗传变异与病例对照研究中的骨质疏松症和低骨密度（BMD）有关。我们现在在一个居住在俄罗斯的欧洲血统（楚瓦什人）的同种族健康家族样本中，检查了 CNR2 多态性与手部骨骼强度的关联。我们发现，两种不同的传递不平衡测试都显示，非同义 CNR2 SNPs 与放射照相手部 BMD 和断裂弯曲阻力指数（BBRI）显著相关。对于这两种测试，在 CNR2 基因座上的其他 SNPs 也获得了非常显著的 p 值（手部 BMD 的范围从 0.007 到 0.008，BBRI 的范围从 0.001 到 0.003）。在进行多次测试校正后，这些关联仍然具有统计学意义。总之，除了 CNR2 多态性与选定的临床相关骨骼部位的低 BMD 相关外，我们现在还使用基于家族的研究设计报告了它们与手部骨骼强度表型的显著关联，这表明 CNR2 基因座的遗传变异对骨骼结构和功能的影响更为广泛。
