title: A functional polymorphism of TIR-domain-containing adaptor protein is not associated with axial spondyloarthritis.
abstract: OBJECTIVE
  A genetic variant of the toll-like receptor (TLR)2/4 adaptor protein TIRAP (single nucleotide polymorphism (SNP) C539T) was identified in a UK and in several African populations. The heterozygous genotype of this SNP has been associated with protection from severe infections. This allele results in an attenuated response to bacterial pathogens. As an exaggerated innate immune response to pathogens has been implicated in spondyloarthritis (SpA) pathogenesis, we analysed if the heterozygous C/T genotype was underrepresented in axial SpA compared with healthy controls.
  
  
  METHODS
  204 patients with axial SpA and 175 population-matched controls were included. SNP C539T was determined with a sequence-specific polymerase chain reaction and direct sequencing.
  
  
  RESULTS
  The frequency of the haplotypes was similar in cases and controls (87% for C and 13% for T in both groups). The C/T genotype, which attenuates TLR signalling, was not underrepresented in cases versus controls (19% in controls vs 24% in cases, p = 0.44). The T/T genotype, was slightly lower in cases than in controls, although this was not significant (3.4% in controls vs 1% in cases, p = 0.15). Within the cases, there were no differences in disease phenotype or activity between patients with the C/C or C/T genotype.
  
  
  CONCLUSIONS
  This study did not show significant associations of SNP S180L of the TLR2/4 adaptor protein TIRAP with axial SpA.
authors: Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors: T
authors: T
authors: Cantaert
authors: M A
authors: MA
authors: Stone
authors: M
authors: M
authors: ter Borg
authors: R
authors: R
authors: Mogg
authors: N
authors: N
authors: De Vries
authors: A G
authors: AG
authors: Wilson
authors: P P
authors: PP
authors: Tak
authors: D
authors: D
authors: Baeten
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000473:pathology
chemical_list: D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human