Identification of a Novel Common Genetic Risk Factor for Lumbar Disk Disease
2001
ContextLumbar 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.ObjectiveTo determine if other collagen IX gene sequence variations play a role
in the pathogenesis of LDD.Design and SettingCase-control study conducted from February 1997 to May 1998 at university
hospitals in Finland.ParticipantsA 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 MeasuresFrequencies 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.ResultsMutation 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.ConclusionThis 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.
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