Introduction: The most well accepted phenotypes of adolescent idiopathic scoliosis (AIS) are relative anterior spinal overgrowth and osteopenia which might because of abnormal endochondral ossification and bone metabolism. Previous linkage studies on familial AIS revealed several candidate chromosomal regions. Asporin (ASPN), tissue inhibitor of metalloproteinases (TIMPs) and insulin-like growth factor-1 receptor (IGF-1R) genes were located in these regions and contribute to bone growth.
Objectives: To investigate the genetic association between ASPN, TIMP-2 and IGF-1R with AIS girls.
Materials and Methods: 222 AIS girls and 210 health girls were recruited. Cobb angle, height, menarche status, curve pattern and Risser sign were recorded. Genetic DNA was extracted from peripheral blood phenol/chloroform method. PCR-RFLP was used for the genotyping.
Results: No significant differences of genotype and allele frequency distribution were found between AIS patients and normal controls in three genes. For the SNP-418G/C (rs8179090) in the promoter region of TIMP-2 gene, patients with GC and CC genotypes showed significantly larger maximal Cobb angles than those with GG genotype.
Conclusion: The SNP-418G/C (rs8179090) in the promoter region of TIMP-2 gene may be associated with curve progression of AIS and TIMP-2 gene is a disease-modifier gene of thoracic AIS. Both ASPN and IGF-1R gene are neither predisposition nor modifier gene of AIS.
Significance: The current study demonstrates that TIMP-2 is not a predisposition gene but a modifier gene of T-AIS and patients with GC and CC genotype have the risk of curve progression and should receive earlier treatment to prevent curve deterioration.