Age-Dependent Association of the COL9A2 TRP2 Allele with Intervertebral Disc Degeneration, Annular Tears and End-Plate Herniations

• (a - Research Grants from Council of Hong Kong)

Background: Low back pain and sciatica are common disabling conditions. They are usually caused by degenerative disc disease (DDD), which is thought to have a genetic predisposition. However, previous studies were not ideal due to a lack of suitable controls and precise phenotype definitions. Magnetic resonance imaging (MRI) is the most accurate way to define DDD. Using this method and a candidate gene approach, we examined the association of DDD with polymorphisms in collagen IX, particularly the association of Gln326Trp in the ±2-chain (Trp2) and Arg103Trp in the ±3-chain (Trp3).

Methods: Lumbar DDD was defined by MRI on 804 Southern Chinese volunteers between 18-55 years, and presence of annular tears, disc and end-plate herniations were also noted. These were correlated with the frequencies of Trp2 and Trp3 alleles. Additionally all three collagen IX genes were scanned for mutations.

Results: The Trp3 allele was absent, while the Trp2 allele was present in 20% of the population. Between 30-39 years of age, Trp2 was associated with a 4-fold increase in the risk of developing annular tears, and between 40-49 years, with a 2.4-fold increase in risk of developing DDD and end-plate herniations. Affected Trp2 individuals had a tendency towards more severe degeneration. No additional mutations were found in the collagen IX genes.

Conclusions: This is the largest-scale population study to date using MRI to precisely define DDD. For the first time, we demonstrated that the Trp2 allele is a significant age-dependent risk factor. These findings suggest that collagen IX is important for intervertebral disc integrity, and that with alterations in its structure the disc becomes more prone to degeneration.

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