title: TLR4 mutations (Asp299Gly and Thr399Ile) are not associated with ankylosing spondylitis.
abstract: BACKGROUND
  Immunoregulatory genes and Gram negative gut bacteria are thought to be important in disease expression in ankylosing spondylitis (AS).
  
  
  OBJECTIVE
  To compare the frequency of two common and functional TLR4 mutations (Asp299Gly, and Thr399Ile) between patients with AS and HLA-B27 healthy controls.
  
  
  METHODS
  The TLR4 genotypes of patients and healthy HLA-B27 controls were determined using allele-specific PCR and restriction fragment length polymorphism analysis. Asp299Gly genotype was determined in 193 patients and 125 HLA-B27 positive controls and Thr399Ile genotype in 184 patients and 113 HLA-B27 controls. Allele frequencies were compared using a chi(2) test of association.
  
  
  RESULTS
  29/193 (15%) patients with AS had a polymorphism in the Asp299 site compared with 18/125 (14.4%) healthy HLA-B27 controls. Of the patients genotyped for the Thr399Ile allele, 29/184 (15.8%) carried the polymorphism compared with 19/113 (16.8%) HLA-B27 controls. No significant difference between the frequencies of the Asp299Gly genotype or the Thr399Ile genotype between patients with AS and healthy HLA-B27 controls was found. No significant difference in allele frequency was found at either site.
  
  
  CONCLUSIONS
  Two common TLR4 polymorphisms, which cause a functional deficiency in host immune response to Gram negative bacteria, are not overrepresented in patients with AS.
authors.affiliation: Centre for Rheumatic Diseases, University Department of Medicine, Queen Elizabeth Building, Glasgow Royal Infirmary University Trust, 10 Alexandra Parade, Glasgow G31 2ER, UK. RosalindA@doctors.org.uk
authors.forename: R
authors.initials: R
authors.lastname: Adam
authors.forename: R D
authors.initials: RD
authors.lastname: Sturrock
authors.forename: J A
authors.initials: JA
authors.lastname: Gracie
mesh_terms: D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015796:HLA-B27 Antigen / Q000276:immunology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018401:Sample Size; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D015796:HLA-B27 Antigen; D051197:Toll-Like Receptor 4