An aggrecan gene polymorphism associated with intervertebral disc degeneration and herniation

Several studies have demonstrated that a genetic factor or familial predisposition contribute to the development of lumbar disc herniation. These studies suggest that there may be a genetic factor in the development of lumbar disc disease. Recently, a polymorphism has been identified in the region of the human aggrecan gene. The purpose of this study was to investigate the relationship between the aggrecan gene polymorphism and lumbar disc disease. Materials and Methods: Sixty-four women, ages 20 to 29 with a mean age of 21.3 years, were the subjects of this study. All patients had MRI analysis in the lumbar spine. The T2-weighted sagittal MRI of the lumbar spine was taken. The degree of disc degeneration was determined according to Schneiderman’s four-grade classification. Disc herniations was evaluated according to MacNab’s classification. Peripheral blood was collected and genomic DNA was extracted from the samples. The polymorphism of the aggrecan gene was detected using a PCR assay. The expressed variable number of tandem repeat (VNTR) polymorphism used in this study occurs in the highly conserved repeat region and results in indivisuals with different length aggrecan core proteins. Results: Thirty two subjects had normal intervertebral discs with high intensity and no herniation. Disc degeneration was observed in 32 subjects. Five subjects demonstrated severe disc degeneration at more than 3 intervertebral levels. A total of 13 alleles have been observed for the aggrecan VNTR and 8 of these were discovered in this study. This distribution was significantly different with an over-representation of the shorter alleles which were 18 and 21 repeats in cases with multi-level disc degeneration and degeneration in the upper lumbar spine. Disc herniation was present in 23 subjects. Fifteen subjects demonstrated protrusion, 7 had extrusion and 1 had sequestration types of herniation. No significant association was found between any of the alleles and the severity and number of disc herniation. Discussion: This study revealed that multi-level and upper lumbar disc degeneration was present in the subjects with shorter VNTR of aggrecan gene. This suggests that the subjects with shorter VNTR of aggrecan gene are at risk for developing disc degeneration at an early age. In contrast, the length of aggrecan VNTR was not related to the existence and the type of disc herniation. Thus, other as yet unspecified and unexplored factors, including the coexistence of several environmental risks and other candidate genes, might contribute to the development of lumbar disc herniation.