Novel Mutations in UTS2R are Associated with Adolescent Idiopathic Scoliosis in the Chinese Population

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 has 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's 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 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.