Aggrecan Gene Polymorphism as a Genetic Marker for Adolescent Idiopathic Scoliosis

Study Design: A case control study using radiographic imaging, PCR assay, and genetic sequencing to investigate the association between aggrecan gene polymorphism and adolescent idiopathic scoliosis (AIS).

Purpose: To analyze the base pair sequence of variable number of tandem repeats (VNTR) region of exon 12 of the aggrecan gene in people with adolescent idiopathic scoliosis.

Summary of Background Data: Recent studies have shown that a genetic factor or familial predisposition contributes to the development of adolescent idiopathic scoliosis. The precise genetic component (candidate gene) related to scoliosis remains undefined. Aggrecan gene is a large proteoglycan that is essential to the stability of cartilage. Our prior research established the relationship between the polymorphism in the aggrecan gene and adolescent idiopathic scoliosis. This polymorphism results in individuals having different length aggrecan core proteins leading to changes in the functional properties of the cartilage. The chondroitin sulfate (CS) domain of aggrecan is encoded by a single large exon 12. The CS domain consists of approximately 120 serine-glycine repeats with a variable number of tandem repeats. However the precise genomic nucleotide sequence in people with adolescent idiopathic scoliosis remains unclear.

Methods: The participants were 30 people under the age of 21 with and without scoliosis. Radiographic imaging was used to evaluate the degree of spinal curvature. 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. The alleles were subsequently sequenced to further characterize the VNTR domain of the participants.

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. Sequencing of the PCR products of the VNTR region demonstrated homology between participants with smaller VNTR domain and large magnitude curves. There was a clear distinction between the base pair nucleotides of the AIS group as compared to controls. In addition, there was also a significant difference between the distribution of alleles and the severity of spinal curvature.

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. The sequencing of the exon 12 further delineates the base pair differences in the AIS group and illustrates the consistent relationship between the smaller VNTR domains and large spinal curvature. Based upon the PCR analysis and base pair sequencing results, the polymorphism of the aggrecan gene is a marker for adolescent idiopathic scoliosis.