title: Association of toll-like receptor 4 variants and ankylosing spondylitis: a case-control study.
abstract: OBJECTIVE
  Functional single nucleotide polymorphisms within the ectoplasmic domain of the Toll-like receptor 4 (TLR4) gene have been shown to result in an endotoxin-hyporesponsive phenotype and aberrant signal transduction for bacterial agonists. TLR4 is in proximity to a genome-wide linkage peak in 9q32-33. Given the proposed function and location of TLR4, we examined the association of 2 functional variants of TLR4 in patients with ankylosing spondylitis (AS) in Newfoundland.
  
  
  METHODS
  In total, 101 AS patients and 100 ethnically matched controls were genotyped, using the Sequenom MassArray platform, for 2 functional variants in the TLR4 gene: Asp299Gly (A/G polymorphism) and Thr399Ile (C/T polymorphism).
  
  
  RESULTS
  The minor allele frequency for the Asp299Gly variant (G) was significantly higher in AS cases compared to controls (7.5% vs 2.6%, respectively; OR 3.10, p = 0.037). The minor allele frequency for the Thr399Ile variant (T) for cases and controls was 7.4% vs 3.0% (OR 2.59, p = 0.071). Haplotype analysis using Haploview noted a higher proportion of GT in the cases (for GT, chi-squared p = 0.023).
  
  
  CONCLUSIONS
  Given the functional role of TLR4 variants in the innate immune system, larger studies are now warranted to elucidate the association of TLR4 variants in AS.
authors.affiliation: Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Tara
authors.initials: T
authors.lastname: Snelgrove
authors.forename: Sooyeol
authors.initials: S
authors.lastname: Lim
authors.forename: Celia
authors.initials: C
authors.lastname: Greenwood
authors.forename: Lynette
authors.initials: L
authors.lastname: Peddle
authors.forename: Sean
authors.initials: S
authors.lastname: Hamilton
authors.forename: Robert
authors.initials: R
authors.lastname: Inman
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4