IGF-I has a pivotal role in bone growth and could be one of the putative disease-modifier genes in AIS. Two SNPs in IGF-I gene promoter region were studied for any association with occurrence of AIS and for their effect on the curve severity among AIS. Methods: 506 AIS girls (Cobb>20°) and 227 age-matched Chinese girls were recruited. The spine (L2-L4) and hip BMD of the subjects were measured by DXA. A subgroup of AIS patients (N=340) who were followed-up to skeletal maturity and the maximum Cobb's angle was recorded. Two SNPs were genotyped by PCR-RFLP (rs5742612 and rs2288377). The chi-square test and one-way ANOVA were used to test the association between genotypes and quantitative parameters, respectively. Results: No association was between the genotypes and the occurrence of AIS and the BMD of the spine and hip. The allelic frequency of T allele was 0.69 in AIS and control. However, the Cobb's angle was higher in patients with the homozygous T allele (Mean Cobb's angle: 38.1° in TT vs 35.9° in TC vs 33.2° in CC group; p=0.04). Discussion: Interestingly, IGF-I polymorphism affects the curve severity of AIS though it was not associated with onset of AIS per se. It indicates that IGF-I may be a disease modifying gene. The importance of IGF-I in skeletal growth makes it a good candidate gene which would play a role in the documented association of rapid growth with curve progression in AIS.