Polymorphism of the Aggrecan Gene as a Marker for Adolescent Idiopathic Scoliosis

Study Design: A case control study using radiographic imaging and a PCR assay to investigate the association between aggrecan gene polymorphism and adolescent idiopathic scoliosis.

Hypothesis: To analyze whether the aggrecan gene polymorphism is related to adolescent idiopathic scoliosis in people under the age of 21.

Summary of Background Data: Recent studies have shown that a genetic factor or familial predisposition contributes to the development of adolescent idiopathic scoliosis. However, the precise genetic component (candidate gene) related to scoliosis remains undefined. Aggrecan is a large proteoglycan that is essential to the stability of cartilage. A polymorphism has been identified in the coding region of the human aggrecan gene in exon 12. This polymorphism results in individuals having different length aggrecan core proteins, which alter the functional properties of cartilage. Although the aggrecan gene has been extensively linked to osteoarthritis, several recent animal model studies have associated mutations in the aggrecan gene to neonatal cervical and lumbar spinal deformity.

Methods: The participants were 30 people between the ages of 7 and 19 with and without scoliosis. Radiographic studies were used to evaluate the degree of spinal curvature, and magnetic resonance imaging to identify other spinal pathology. Genomic deoxyribonucleic acid was extracted from all participants. A polymerase chain reaction assay was carried out to detect the alleles of the aggrecan gene. The association of adolescent idiopathic scoliosis with the distribution of the aggrecan gene alleles was analyzed.

Results: Polymerase chain reaction findings showed an increase of alleles with smaller numbers of repeats in subjects with adolescent idiopathic scoliosis as compared to the control group. In addition, there was a significant difference between the distribution of alleles and the severity of spinal curvature. There was no significant association found between the number and size of alleles as related to the age of the patient.

Conclusion: Our results demonstrate that patients with adolescent idiopathic scoliosis have shorter variable numbers of tandem repeat length in exon 12 of the aggrecan gene. These findings strongly suggest that people under the age of 21 with shorter variable numbers of tandem repeat length of the aggrecan gene have a risk of developing scoliosis. The polymorphism of the aggrecan gene can be used as a marker for adolescent idiopathic scoliosis.