School of Medical Sciences, Griffith University, Gold Coast, Queensland, Australia.
PLoS One. 2013 Sep 23;8(9):e72740. doi: 10.1371/journal.pone.0072740. eCollection 2013.
Runt related transcription factor 2 (RUNX2) is a key regulator of osteoblast differentiation. Several variations within the RUNX2 gene have been found to be associated with significant changes in BMD, which is a major risk factor for fracture. In this study we report that an 18 bp deletion within the polyalanine tract (17A>11A) of RUNX2 is significantly associated with fracture. Carriers of the 11A allele were found to be nearly twice as likely to have sustained fracture. Within the fracture category, there was a significant tendency of 11A carriers to present with fractures of distal radius and bones of intramembranous origin compared to bones of endochondral origin (p = 0.0001). In a population of random subjects, the 11A allele was associated with decreased levels of serum collagen cross links (CTx, p = 0.01), suggesting decreased bone turnover. The transactivation function of the 11A allele showed a minor quantitative decrease. Interestingly, we found no effect of the 11A allele on BMD at multiple skeletal sites. These findings suggest that the 11A allele is a biologically relevant polymorphism that influences serum CTx and confers enhanced fracture risk in a site-selective manner related to intramembranous bone ossification.
runt 相关转录因子 2（RUNX2）是成骨细胞分化的关键调节因子。已经发现 RUNX2 基因中的几个变异与 BMD 的显著变化有关，BMD 是骨折的主要危险因素。在这项研究中，我们报告了 RUNX2 多聚丙氨酸链内的 18bp 缺失（17A>11A）与骨折显著相关。携带 11A 等位基因的个体发生骨折的可能性几乎是携带 17A 等位基因的个体的两倍。在骨折类别中，与软骨内起源的骨骼相比，11A 携带者出现远端桡骨和膜内起源骨骼骨折的趋势更为明显（p=0.0001）。在随机人群中，11A 等位基因与血清胶原交联物（CTX）水平降低有关（p=0.01），表明骨转换减少。11A 等位基因的转录激活功能显示出轻微的定量下降。有趣的是，我们没有发现 11A 等位基因对多个骨骼部位的 BMD 有影响。这些发现表明，11A 等位基因是一种具有生物学意义的多态性，它影响血清 CTx，并以与膜内骨骨化相关的选择性方式赋予增强的骨折风险。
