Expression of the trp2 allele of COL9A2 is associated with alterations in the mechanical properties of human intervertebral discs

Study Design. Biomechanical study into the association between genetic polymorphism in COL9A2 and mechanical properties of human nucleus pulposus. Objective. To examine whether there is an association between genetic polymorphism in a structural gene, and alterations in the mechanical properties of the intervertebral discs that may predispose to disc degeneration. Summary of Background Data. Genetic studies have demonstrated that a polymorphism (Trp2 allele) in COL9A2 coding for alpha 2 chain of collagen IX predisposes the individual to disc degeneration. The mechanism of this predisposition is not known. Methods. Blood and whole disc samples were retrieved from adolescents and young adults during scoliosis surgery, degenerated discs were retrieved from patients with back pain during anterior spinal fusion. Anulus fibrosus and nucleus pulposus from a set of the scoliosis discs were used to perform immunohistochemistry to demonstrate the presence of collagen IX in the scoliosis discs. For the remaining samples, DNA was extracted from blood to determine the Trp2 status by sequencing. Nondegenerated (Trp2-), nondegenerated (Trp2-), and degenerated (Trp2-) nucleus pulposus samples were tested in confined compression. Swelling pressure and compressive modulus were measured and compared between groups. Results. Positive staining of collagen IX was detected in both anulus fibrosus and nucleus pulposus sections confirming its presence in the scoliosis discs. The mean swelling pressure and compressive modulus values of 6 nondegenerated (Trp2-) samples (swelling pressure = 0.0019 MPa, compressive modulus = 0.97 MPa) were significantly lower (P < 0.05) than those of the 6 nondegenerated (Trp2+) samples (swelling pressure = 0.015 MPa; compressive modulus = 1.89 MPa). Conclusion. This is the first study to demonstrate an association between the Trp2 allele and disc mechanics, thus relating genetic variations and debilitating mechanical alterations that may ultimately result in intervertebral disc degeneration.