Adolescent idiopathic scoliosis is a structural curvature of the spine that affects millions of children in the world [
1‐
3]. Although numerous studies have been performed to investigate the etiology of AIS, there was still a limited understanding of its pathogenesis [
4‐
7]. As a complex multi-factorial disease, AIS was believed to be resulted from the interaction among multiple genetic loci as well as environmental factors [
8,
9]. Through genetic linkage analysis, a few susceptible loci have been proposed to be closely related to AIS [
10‐
12]. Subsequently, more predisposition genes of AIS were identified through association studies, including estrogen receptor 1 (ESR1) [
13,
14], estrogen receptor 2 (ESR2) [
15], matrilin 1 (MATN1) [
16], melatonin receptor 1B (MTNR1B) [
17], tryptophan hydroxylase 1 (TPH1) [
18], interleukin-6 (IL-6) [
19,
20], C17orf67 and DOT1L [
21]. In recent years, the pathogenesis of AIS was further investigated through genome-wide association studies (GWASs). Sharma et al. [
22] reported a strong association between the CHL1 gene and AIS in 419 white families. GWAS in Japanese population confirmed that the ladybird homeobox 1 (LBX1) gene and G protein—coupled receptor 126 (GPR126) gene were significantly associated with the development of AIS [
23,
24]. Specifically, the LBX1 gene was confirmed as the susceptibility gene of AIS by a large-scale study in the European population [
25].
Although the genetic background of AIS has been investigated extensively through genetic association study, spurious results may be produced along with those intriguing findings. As a well established AIS susceptibility gene in the Caucasian population, the CHL1 gene failed to be replicated in the Chinese Han population [
26]. The ESR1 gene was firstly confirmed to be associated with AIS in the Japanese population and later successfully validated in the Chinese and the Caucasian population [
13,
14,
27,
28]. Interestingly, this association was not supported by other 3 replication studies separately performed in the Asian and the Caucasian population [
29‐
31]. Takahashi et al. [
30,
32] failed to validate previously reported susceptible genes of AIS in the Japanese population, including ESR2, MTNR1B, TPH1 and MATN1. Collectively, there exists a significant divergence between the Asian and the Caucasian populations regarding the association of susceptible genes with the pathogenesis of AIS. Moreover, this divergence can even exist in the same population. Therefore, the large-scale replication study is warranted to validate previously reported susceptible genes of AIS.
Recently, Ryzhkov et al. [
33] reported that the genetic polymorphism of the transforming growth factor beta-1 (TGFB1) gene was significantly associated with the onset of AIS as well as the curve severity in the Russian population. Interestingly, mutations in TGFB family genes can lead to syndromic forms of scoliosis such as Marfan and Loeys Dietz Syndrome [
34,
35]. It is therefore possible that common variants of TGFB1 can be associated with AIS through similar pathway. To our knowledge, there is still a lack of knowledge concerning the association of TGFB1 gene with AIS in the Chinese population. The primary purpose of this study was to replicate the relationship between the TGFB1 gene and the susceptibility of AIS in the Chinese population, and to further describe its association with the curve severity.