Novel Mutations in UTS2R are Associated with Adolescent Idiopathic Scoliosis in the Chinese Population
Novel Mutations in UTS2R are Associated with Adolescent Idiopathic Scoliosis in the Chinese Population
复制标题
UTS2R的新突变与中国人群中青少年特发性脊柱侧弯有关
DOI：
10.1097/brs.0000000000003786
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发表时间：
2021-03-01
期刊：
影响因子：
3
通讯作者：
Zhu, Zezhang
中科院分区：
文献类型：
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作者：
Dai, Zhicheng;Wang, Yuwen;Zhu, Zezhang
研究设计。病例对照研究。目标。目的探讨尾加压素II(UTS2)信号与中国汉族青少年特发性脊柱侧凸(AIS)易感性的关系。背景数据摘要。通过对斑马鱼的研究，发现由脑脊液流量受损引起的UTS2信号异常与特发性脊柱侧弯的发生有关。此外，尾加压素II受体(UTS2R)的突变被报道会导致斑马鱼严重的脊柱侧弯。尽管在动物模型中提出了证据，但对于UTS2信号相关基因在AIS中的作用仍然缺乏了解。方法：研究方法。在发现阶段，对200例AIS患者和200例健康对照进行了UTS2、UTS2R和UTS2D基因外显子测序。在另外1000名AIS患者和1000名对照中，通过等位基因特异的多重连接酶检测反应，对新发现的突变进行了进一步的基因分型。对36例AIS患者和36例年龄匹配的先天性脊柱侧凸患者进行基因表达分析。组间基因分型资料比较采用卡方检验。基因表达分析采用t检验。结果。两个新的突变(rs11654140，c.51T>；C；rs568196624，c.1146C>；G)与AIS的发生有关。Rs11654140的C等位基因和rs568196624的G等位基因与AIS的危险性显著相关(rs11654140为1.5%对0.5%，优势比=3.02，P=0.01；rs568196624为1.41%对0.58%，优势比=2.29，P=0.04)。AIS组UTS2RmRNA表达显著高于对照组(0.059+/-0.015比0.035+/-0.013，P<0.01)。结论。UTS2R罕见突变与AIS显著相关。AIS患者UTS2R表达明显增加。UTS2信号在AIS发生发展中的作用值得进一步研究。
Study Design. A case-control study. Objectives. To investigate the association of urotensin II (UTS2) signals with the susceptibility of adolescent idiopathic scoliosis (AIS) in the Chinese Han population. Summary of Background Data. Dysregulated UTS2 signals induced by impaired cerebrospinal fluid flow have been implicated in the development of idiopathic scoliosis through studies on zebrafish. Furthermore, mutations in urotensin II receptor (UTS2R) were reported to cause severe scoliosis in zebrafish. In spite of the evidence presented in animal models, there is still a lack of knowledge concerning the role of UTS2 signaling related genes in AIS. Methods. In the discovery stage, exons of UTS2, UTS2R, and UTS2D were sequenced for 200 AIS patients and 200 healthy controls. Newly identified mutations were further genotyped in another independent cohort of 1000 AIS patients and 1000 controls by allelic-specific multiple ligase detection reactions. Gene expression analysis was performed in 36 AIS patients and 36 age-matched congenital scoliosis patients. The Chi-square test was used to compare the genotyping data between the groups. Gene expression analysis was compared with the Student t test. Results. Association between two novel mutations (rs11654140, c.51T > C; rs568196624, c.1146C > G) and the development of AIS was identified. Allele C of rs11654140 and allele G of rs568196624 were significantly associated with the risk of AIS (1.5% vs. 0.5%, odds ratio = 3.02, P = 0.01 for rs11654140; 1.41% vs. 0.58%, odds ratio = 2.29, P = 0.04 for rs568196624). The mRNA expression of UTS2R in the AIS group was significantly higher as compared with that in the control group (0.059 +/- 0.015 vs. 0.035 +/- 0.013, P < 0.01). Conclusions. Rare mutations in UTS2R were significantly associated with AIS. Expression of UTS2R was significantly increased in AIS patients. The role of UTS2 signaling in the development of AIS is worthy of further investigation.