Identification of a novel common genetic risk factor for lumbar disk disease

Context Lumbar disk disease (LDD) is one of the most common musculoskeletal diseases, with a prevalence of about 5%, A tryptophan (Trp) allele (Trp2) was recently discovered in the COL9A2 gene that is associated with dominant ly inherited LDD but is only present in about 4% of Finnish patients with L DD. Objective To determine if other collagen IX gene sequence variations play a role in the pathogenesis of LDD. Design and Setting Case-control study conducted from February 1997 to May 1 998 at university hospitals in Finland. Participants A total of 171 individuals with LDD (evaluated clinically and by magnetic resonance imaging or computed tomography) and 321 controls with out LDD (186 healthy individuals, 83 patients with primary osteoarthritis, 31 with rheumatoid arthritis, and 21 with chondrodysplasias). Main Outcome Measures Frequencies of sequence variations covering the entir e coding sequences and exon boundaries of the collagen IX genes, COL9A1, CO L9A2, and COL9A3, which code for the alpha1, alpha2, and alpha3 chains of t he protein, detected by conformation-sensitive gel electrophoresis and conf irmed by sequencing, compared between individuals with and without LDD, Results Mutation analysis of all 3 collagen IX genes resulted in identifica tion of an Arg103 --> Trp (arginine --> tryptophan) substitution in the alp ha3 chain (Trp3 allele). The frequency of the Trp3 allele was 12.2% in LDD cases, excluding 7 individuals who were carriers of the previously identifi ed Gln326 --> Trp (glutamine --> tryptophan) substitution in the a2 chain ( Trp2 allele), and was 4.7% among controls. The difference in the frequency was statistically significant (P = .000013). Presence of at least 1 Trp3 al lele increases risk of LDD about 3-fold. Conclusion This study led to the identification of a novel common genetic r isk factor for LDD, confirming that genetic risk factors likely play a sign ificant role in LDD.