title: Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis.
abstract: BACKGROUND
  Degenerative lumbar spinal stenosis (LSS) is usually caused by disc herniation or degeneration. Several genetic factors have been implicated in disc disease. Tryptophan alleles in COL9A2 and COL9A3 have been shown to be associated with lumbar disc disease in the Finnish population, and polymorphisms in the vitamin D receptor gene (VDR) (FokI and TaqI), the matrix metalloproteinase-3 gene (MMP-3) and an aggrecan gene (AGC1) VNTR have been reported to be associated with disc degeneration. In addition, an IVS6-4 a>t polymorphism in COL11A2 has been found in connection with stenosis caused by ossification of the posterior longitudinal ligament in the Japanese population.
  
  
  OBJECTIVE
  To study the role of genetic factors in LSS.
  
  
  METHODS
  29 Finnish probands were analysed for mutations in the genes coding for intervertebral disc matrix proteins, COL1A1, COL1A2, COL2A1, COL9A1, COL9A2, COL9A3, COL11A1, COL11A2, and AGC1. VDR and MMP-3 polymorphisms were also analysed. Sequence variations were tested in 56 Finnish controls.
  
  
  RESULTS
  Several disease associated alleles were identified. A splice site mutation in COL9A2 leading to a premature translation termination codon and the generation of a truncated protein was identified in one proband, another had the Trp2 allele, and four others the Trp3 allele. The frequency of the COL11A2 IVS6(-4) t allele was 93.1% in the probands and 72.3% in controls (p = 0.0016). The differences in genotype frequencies for this site were less significant (p = 0.0043).
  
  
  CONCLUSIONS
  Genetic factors have an important role in the pathogenesis of LSS.
authors.affiliation: Collagen Research Unit, Biocentre and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland.
authors.forename: N
authors.initials: N
authors.lastname: Noponen-Hietala
authors.forename: E
authors.initials: E
authors.lastname: Kyllönen
authors.forename: M
authors.initials: M
authors.lastname: Männikkö
authors.forename: E
authors.initials: E
authors.lastname: Ilkko
authors.forename: J
authors.initials: J
authors.lastname: Karppinen
authors.forename: J
authors.initials: J
authors.lastname: Ott
authors.forename: L
authors.initials: L
authors.lastname: Ala-Kokko
mesh_terms: D000328:Adult; D000368:Aged; D053674:Aggrecans; D015139:Blotting, Southern; D024081:Collagen Type IX / Q000235:genetics*; D024161:Collagen Type XI / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D017423:Sequence Analysis, RNA; D013130:Spinal Stenosis / Q000235:genetics*
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D024081:Collagen Type IX; D024161:Collagen Type XI; D011509:Proteoglycans; D018167:Receptors, Calcitriol