title: The role of collagen IX tryptophan polymorphisms in symptomatic intervertebral disc disease in Southern European patients.
abstract: METHODS
  We conducted a cross-sectional, genotyping study of intervertebral disc disease patients and controls.
  
  
  OBJECTIVE
  To determine the contribution of COL9A2 and COL9A3 Tryptophan polymorphisms to intervertebral disc disease development in a genetically heterogeneous, Southern European population compared to previous Finnish studies.
  
  
  BACKGROUND
  The COL9A2 and COL9A3 genes encode the alpha2 and alpha3 chains of Collagen IX. Recent Finnish studies suggest that a tryptophan polymorphism in the COL9A2 gene (Trp2) results in hereditary intervertebral disc disease, whereas a similar tryptophan mutation in COL9A3 (Trp3) conveys a 3-fold risk of intervertebral disc disease.
  
  
  METHODS
  We studied 105 symptomatic patients with radiographically and/or surgically proven lumbar (98%, n = 103) or cervical (2%, n = 2) intervertebral disc disease and 102 age-matched controls without spinal complaints from hospitals in Athens, Greece. Intervertebral disc disease was defined as significant disc herniation resulting in persistent back or leg pain. We genotyped all patients for COL9A2 and COL9A3 allele variations using a polymerase chain reaction-based technique.
  
  
  RESULTS
  None of our patients had the Trp2 allele. Consistent with previous Finnish findings, more Greek intervertebral disc disease cases (8.6%) than controls (4.9%) had at least 1 Trp3 allele, but this difference did not reach statistical significance (P = 0.293). The allele frequency of the Trp3 mutation was significantly higher among previously studied Finnish patients with intervertebral disc disease (12.3%) than among the Southern European patients with intervertebral disc disease in our study (4.3%), P = 0.001.
  
  
  CONCLUSIONS
  The differences in Trp allele frequency we found between Greek and Finnish patients with intervertebral disc disease most likely represent true differences in polymorphism prevalence between the respective populations. The 2 previously described Trp alleles in COL9A2 and COL9A3 are likely to be less significant susceptibility factors for intervertebral disc disease development in Southern European populations.
authors.affiliation: Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Stefanos N
authors.initials: SN
authors.lastname: Kales
authors.forename: Athena
authors.initials: A
authors.lastname: Linos
authors.forename: Christos
authors.initials: C
authors.lastname: Chatzis
authors.forename: Yang
authors.initials: Y
authors.lastname: Sai
authors.forename: Maria
authors.initials: M
authors.lastname: Halla
authors.forename: Georgios
authors.initials: G
authors.lastname: Nasioulas
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000328:Adult; D024081:Collagen Type IX / Q000737:chemistry / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006115:Greece; D006801:Humans; D007405:Intervertebral Disc Displacement / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D014364:Tryptophan / Q000235:genetics*
chemical_list: D024081:Collagen Type IX; D014364:Tryptophan