Genetic Variant of TBX1 Gene Is Functionally Associated With Adolescent Idiopathic Scoliosis in the Chinese Population

Study Design. A genetic association study. Objective. The aim of this study was to investigate whether rs1978060 of TBX1 gene was a susceptible locus of adolescent idiopathic scoliosis (AIS) in the Chinese Han population and to better define the functional role of TBX1 in the development and progression of AIS. Summary of Background Data. A recent genome-wide association study reported a novel susceptible locus in TBX1 gene, which was associated with the development of AIS in the Japanese population. However, there is a paucity of knowledge concerning the functional role of TBX1 in the Chinese AIS population. Methods. The SNP rs1978060 was genotyped in 1725 female AIS patients and 2600 healthy controls. Paraspinal muscle samples were collected from 30 AIS patients and 26 age-matched congenital scoliosis (CS) patients for the analysis of tissue expression. The differences of genotype and allele distributions between the patients and the controls were calculated using the chi(2) test. The Pearson correlation analysis was carried out to investigate the relation between the expression of the PAX1 gene and the curve severity. Results. SNP rs1978060 was significantly associated with the susceptibility of AIS. Allele G of rs1978060 could significantly add to the risk of AIS with an odds ratio of 1.12. The tissue expression of TBX1 was obviously decreased in AIS patients. There was a remarkable correlation between the curve magnitude and the TBX1 expression (r = -0.519, P = 0.003). Conclusion. The association between TBX1 and the susceptibility of AIS was successfully replicated in the Chinese population. Moreover, rs1978060 may be a functional variant regulating the expression of TBX1. More studies were warranted to explore the functional role of TBX1 in the onset and progression of AIS.