Identification of a Novel Common Genetic Risk Factor for Lumbar Disk Disease

• Published in: JAMA : the journal of the American Medical Association 2001-04, Vol.285 (14), p.1843-1849
• Main Authors: Paassilta, Petteri, Lohiniva, Jaana, Göring, Harald H. H, Perälä, Merja, Räinä, S. Susanna, Karppinen, Jaro, Hakala, Markku, Palm, Tiina, Kröger, Heikki, Kaitila, Ilkka, Vanharanta, Heikki, Ott, Jürg, Ala-Kokko, Leena
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Arginine; Biological and medical sciences; Case-Control Studies; Collagen - genetics; Collagen Type IX; Disease; Diseases of the osteoarticular system; Diseases of the spine; DNA Mutational Analysis; Electrophoresis; Finland; Genes; Genetic Predisposition to Disease; Health risk assessment; Humans; Intervertebral Disc Displacement - diagnosis; Intervertebral Disc Displacement - genetics; Lumbar Vertebrae; Magnetic Resonance Imaging; Medical research; Medical sciences; Middle Aged; Point Mutation; Polymerase Chain Reaction; Risk Factors; Spine; Tomography, X-Ray Computed; Tryptophan - genetics
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.285.14.1843

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 dominantly inherited LDD but is only present in about 4% of Finnish patients with LDD. 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 1998 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 without 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 entire coding sequences and exon boundaries of the collagen IX genes, COL9A1, COL9A2, and COL9A3, which code for the α1, α2, and α3 chains of the protein, detected by conformation-sensitive gel electrophoresis and confirmed by sequencing, compared between individuals with and without LDD. RESULTS Mutation analysis of all 3 collagen IX genes resulted in identification of an Arg103→Trp (arginine→tryptophan) substitution in the α3 chain (Trp3 allele). The frequency of the Trp3 allele was 12.2% in LDD cases, excluding 7 individuals who were carriers of the previously identified Gln326→Trp (glutamine→tryptophan) substitution in the α2 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 allele increases risk of LDD about 3-fold. CONCLUSION This study led to the identification of a novel common genetic risk factor for LDD, confirming that genetic risk factors likely play a significant role in LDD.