UTS2R 中的新突变与中国青少年特发性脊柱侧凸有关。
Novel Mutations in UTS2R are Associated with Adolescent Idiopathic Scoliosis in the Chinese Population.
机构信息
Department of Spine Surgery, the Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing & Hong Kong, China.
出版信息
Spine (Phila Pa 1976). 2021 Mar 1;46(5):E288-E293. doi: 10.1097/BRS.0000000000003786.
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.Level of Evidence: N/A.
研究设计
病例对照研究。
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。
背景资料概要
通过对斑马鱼的研究表明，脑脊液流动障碍引起的 UTS2 信号失调可能导致特发性脊柱侧凸的发生。此外，UTS2 受体（UTS2R）的突变被报道可导致斑马鱼严重脊柱侧凸。尽管在动物模型中提供了证据，但关于 UTS2 信号相关基因在 AIS 中的作用仍知之甚少。
方法
在发现阶段，对 200 例 AIS 患者和 200 例健康对照者的 UTS2、UTS2R 和 UTS2D 的外显子进行测序。通过等位基因特异性多重连接检测反应，对另一个独立的 1000 例 AIS 患者和 1000 例对照者的新发现突变进行进一步基因分型。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。采用卡方检验比较组间的基因分型数据。基因表达分析与学生 t 检验进行比较。
结果
发现两个新突变（rs11654140，c.51T>C；rs568196624，c.1146C>G）与 AIS 的发生有关。rs11654140 的等位基因 C 和 rs568196624 的等位基因 G 与 AIS 的发病风险显著相关（1.5%比 0.5%，优势比=3.02，P=0.01；1.41%比 0.58%，优势比=2.29，P=0.04）。与对照组相比，AIS 组 UTS2R 的 mRNA 表达显著升高（0.059±0.015 比 0.035±0.013，P<0.01）。
结论
UTS2R 的罕见突变与 AIS 显著相关。AIS 患者 UTS2R 的表达显著增加。UTS2 信号在 AIS 发生发展中的作用值得进一步研究。
证据水平
N/A。
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