Genetic Variants of CHD7 Are Associated with Adolescent Idiopathic Scoliosis
Genetic Variants of CHD7 Are Associated with Adolescent Idiopathic Scoliosis
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DOI：
10.1097/brs.0000000000003857
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发表时间：
2020-12
期刊：
影响因子：
3
通讯作者：
Zhichong Wu;Z. Dai;Wang Yuwen;Zhen Liu;Y. Qiu;J. Cheng;Ze-zhang Zhu;Leilei Xu
中科院分区：
文献类型：
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作者：
Zhichong Wu;Z. Dai;Wang Yuwen;Zhen Liu;Y. Qiu;J. Cheng;Ze-zhang Zhu;Leilei Xu
补充数字内容可在文本“研究设计”中找到。病例对照关联研究。目标.本研究旨在探讨CHD7基因是否与中国汉族青少年特发性脊柱侧凸（adolescent idiopathic scoliosis，AIS）相关，并进一步探讨CHD7基因在青少年特发性脊柱侧凸（adolescent idiopathic scoliosis，AIS）发生发展中的作用。背景数据总结。几项研究探讨了欧洲血统患者中CHD7与脊柱侧凸的相关性，但结果不一致。在中国汉族人群中，缺乏CHD7与AIS相关性的研究。方法.在965名AIS患者和976名健康对照中对CHD7内的变异体进行基因分型。对96例AIS患者进行了全外显子组测序。收集43例AIS患者和38例腰椎间盘突出症患者的椎旁肌进行基因表达评估。组间比较采用χ 2检验进行基因分型数据或Student t检验进行组织表达。采用Pearson相关分析确定CHD7表达与临床表型的关系。结果. CHD 7基因rs121434341变异与AIS显著相关。AIS患者G等位基因频率显著高于健康对照组（2.89%vs.1.57%，P = 0.0018），比值比为1.89。在一名患者中发现了一种影响正常剪接的致病性突变。此外，AIS患者CHD 7的表达水平明显低于对照组（0.0008437 ± 0.00004583 vs.0.001129 ± 0.00003773，P <0.001），且CHD 7表达与骨矿物质含量正相关（P = 0.036，r = 0.32）。结论CHD7的遗传变异与AIS显著相关。CHD7表达降低可能参与AIS患者骨量异常的发生。CHD7在AIS发病机制中的作用有待进一步研究。证据等级：3
Supplemental Digital Content is available in the text Study Design. A case–control association study. Objectives. The aim of this study was to investigate whether CHD7 was associated with adolescent idiopathic scoliosis in Chinese Han population and to further explore the functional role of CHD7 in the development of adolescent idiopathic scoliosis (AIS). Summary of Background Data. Several studies have explored the association of CHD7 with scoliosis in patients of European descent, while the results were inconsistent. There was a lack of study investigating the association of CHD7 with AIS in Chinese Han population. Methods. Variants within CHD7 were genotyped in 965 AIS patients and 976 healthy controls. Whole exome sequencing was performed in 96 AIS patients. Paraspinal muscles of 43AIS patients and 38 lumbar disc herniation patients were collected for the evaluation of the gene expression. Intergroup comparison was performed with the χ2 test for genotyping data or Student t test for tissue expression. The relationship of CHD7 expression with clinical phenotypes was determined by the Pearson correlation. Result. Variant rs121434341 of CHD7 was significantly associated with AIS. AIS patients were found to have a remarkable higher frequency of allele G when compared with healthy controls (2.89% vs. 1.57%, P = 0.0018), with an odds ratio value of 1.89. A pathogenic mutation affecting normal splicing was identified in a patient. Moreover, the expression level of CHD7 in AIS patients was significantly lower than in the controls (0.0008437 ± 0.00004583 vs. 0.001129 ± 0.00003773, P < 0.001), and CHD7 expression was positively correlated with bone mineral contents (P = 0.036, r = 0.32). Conclusion. Genetic variants of CHD7 were significantly associated with AIS. Moreover, the decreased expression of CHD7 may be involved in the abnormal bone mass of AIS patients. Further studies are warranted to investigate the functional role of CHD7 in the pathogenesis of AIS. Level of Evidence: 3