Genetic variant of COL11A2 gene is functionally associated with developmental dysplasia of the hip in Chinese Han population
Genetic variant of COL11A2 gene is functionally associated with developmental dysplasia of the hip in Chinese Han population
复制标题
COL11A2基因的遗传变异与中国汉族人群髋关节发育不良存在功能相关性
DOI：
10.18632/aging.103040
复制
发表时间：
2020-05-15
期刊：
影响因子：
5.2
通讯作者：
Zhang，Yuxin
中科院分区：
文献类型：
--
作者：
Xu，Renjie;Jiang，Xin;Zhang，Yuxin
目的：髋关节发育不良（DDH）是一种常见的骨骼疾病。本研究旨在证明DDH与COL11A2基因多态性rs9277935之间的关联。结果：两组隐性模型（TT+GT vs. GG）基因型分布差异有统计学意义（P=0.017）。在女性患者中，G小等位基因频率显著高于男性（0.49比0.43,p=0.024）， GG基因型分布显著高于女性（p=0.006）。DDH患者COL11A2表达明显低于对照组。此外，rs9277935基因型TT的DDH患者COL11A2的表达明显高于基因型GG的患者，COL11A2在体外表现出软骨形成的特性。结论：COL11A2基因rs9277935多态性是中国汉族DDH患者COL11A2基因表达及软骨形成特性的功能变异。方法：对945例DDH患者（350例放射学证实的DDH患者和595例健康对照）进行病例对照的候选基因关联研究。比较患者与对照组髋关节组织COL11A2表达的差异。利用荧光素酶活性评估rs9277935基因表达Col11a2的等位基因差异。Col11a2信号传导对骨髓间充质干细胞的成软骨作用也在体外进行了研究。
Objectives: Developmental dysplasia of the hip (DDH) is a common skeletal disorder. This study was conducted to demonstrate the association between DDH and a polymorphism rs9277935 of COL11A2 gene. Results: A significant difference in genotype distribution in a recessive model (TT+GT vs. GG) between two groups (P=0.017) was demonstrated. Analysis in female patients showed significantly greater frequency of minor allele G(0.49 vs. 0.43, p=0.024) and significantly higher distribution of GG genotype (p=0.006). DDH patients were found to have significantly lower COL11A2 expression than controls. Moreover, DDH patients with rs9277935 genotype TT have a significantly increased expression of COL11A2 than those with genotype GG. COL11A2 demonstrated chondrogenic properties in vitro. Conclusion: Polymorphism rs9277935 of gene COL11A2 is a functional variant regulating the expression and the chondrogenic properties of COL11A2 in DDH in Chinese Han population. Methods: A case-control candidate gene association study was conducted in 945 patients (350 radiologically confirmed DDH patients and 595 healthy controls). Difference of COL11A2 expression in hip joint tissue was compared between the patients and the controls. Allelic difference in Col11a2 expression by rs9277935 was assessed with luciferase activity. Chondrogenic effects of Col11a2 signaling on BMSCs were also determined in vitro.