STUDY DESIGN: A genetic association study to comprehensively investigate 
variations of neurotrophin 3 (NTF3) gene polymorphisms in a Chinese Han 
population.
OBJECTIVE: To explore whether the NTF3 gene polymorphisms are associated with 
the susceptibility, curve severity, or bracing effectiveness of adolescent 
idiopathic scoliosis (AIS).
SUMMARY OF BACKGROUND DATA: Scoliosis has developed in mice with NTF3 deficiency 
in previous studies. Increased expression of NTF3 mRNA was detected in the 
paravertebral muscle in AIS. Moreover, linkage study has defined a novel AIS 
locus on chromosome 12p while NTF3 gene is located exactly in this interval. All 
evidence indicates a potential role of NTF3 in the pathogenesis of AIS. As for 
brace treatment of AIS, continuous sensory stimulation caused by an orthosis 
could help awareness of body misalignment and trigger curve correction through 
postural reflex. While NTF3 gene is tightly associated with proprioceptive 
feedback mechanism to adjust postural control, we hypothesized NTF3 as a 
potential candidate gene associated with the bracing effectiveness.
METHODS: A total of 362 AIS patients and 377 age-matched healthy controls were 
recruited. Two single-nucleotide polymorphisms (SNPs) were selected on the basis 
of the Chinese data from the HapMap project, and genotyping was carried out by 
polymerase chain reaction-restriction fragment length polymorphism for each SNP, 
respectively. Case-control study and case-only study were performed to define 
the contribution of NTF3 gene polymorphisms to predisposition and disease 
severity of AIS. Another subgroup of 120 skeletally immature AIS patients who 
received continuous brace treatment for minimal 2 years was genotyped, and 
bracing effectiveness was assessed to determine its association with NTF3 gene 
polymorphisms.
RESULTS: The genotype and allele frequency distribution were similar between AIS 
and normal control for these 2 SNPs (χ² test: P > 0.05). For SNP rs11063714 in 
the promoter region of NTF3 gene, AIS patients with AA genotype showed 
significantly lower mean maximum Cobb angle than the patients with AG or GG 
genotypes (analysis of variance: P = 0.008). In addition, skeletally immature 
bracing AIS patients with AA genotype possessed significantly higher successful 
ratio of brace treatment compared with GG genotype (χ² test: P = 0.043). For SNP 
rs1805149, no significant association with predisposition or curve severity was 
detected.
CONCLUSION: The NTF3 gene polymorphisms are not associated with the occurrence 
of AIS, but the promoter polymorphism (rs11063714) is associated with the curve 
severity, implicating an alleviating role of NTF3 in the curve progression of 
AIS. In addition, the promoter polymorphism is also associated with brace 
responsiveness. These findings indicated that NTF3 gene might be a 
disease-modifying gene of AIS.