title: TIRAP Ser180Leu polymorphism is associated with Behcet's disease.
abstract: OBJECTIVE
  The initiating cause of Behçet's disease (BD) is unknown, but an aberrant response to infection has been suggested. In this study, single nucleotide polymorphisms in Toll-like receptors (TLRs) and associated molecules that have a sentinel function at mucosal surfaces were analysed in patients with BD.
  
  
  METHODS
  TLR expression was determined by immunohistochemistry in buccal mucosal tissue from patients with BD, in tissue from patients with lichen planus (LP) or pyogenic granuloma (PG) as disease controls, or from healthy individuals. Using SSP-PCR we analysed SNP in CD14, TLR2, TLR4 and TIRAP (TIR domain-containing adaptor protein) in patients with BD from different geographical regions.
  
  
  RESULTS
  TLR expression was increased in buccal lesions from patients with BD compared with healthy controls; however, a similar increase was seen in lesion tissue from patients with LP or PG, suggesting that this was a generalized inflammatory response as opposed to a BD-specific response. SNP analysis showed no association between CD14, TLR2 or TLR4 polymorphisms. However, TIRAP 180Leu was significantly associated with BD in UK, but not Middle Eastern, patients.
  
  
  CONCLUSIONS
  TLR expression showed no difference in tissue from patients with BD compared with either disease or healthy controls. Likewise, SNPs in TLR genes were no different from healthy controls. The association with the increased function variant of TIRAP suggests that encounter with a pathogen at mucosal sites will lead to increased cytokine production and tissue damage with persistence of mucosal lesions.
authors.affiliation: Academic Unit of Ophthalmology, School of Immunity and Infection, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.
authors.forename: Omar
authors.initials: O
authors.lastname: Durrani
authors.forename: Katherine
authors.initials: K
authors.lastname: Banahan
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Sheedy
authors.forename: Laura
authors.initials: L
authors.lastname: McBride
authors.forename: Eldad
authors.initials: E
authors.lastname: Ben-Chetrit
authors.forename: Kathryn
authors.initials: K
authors.lastname: Greiner
authors.forename: Robert W
authors.initials: RW
authors.lastname: Vaughan
authors.forename: Elli
authors.initials: E
authors.lastname: Kondeatis
authors.forename: John
authors.initials: J
authors.lastname: Hamburger
authors.forename: Farida
authors.initials: F
authors.lastname: Fortune
authors.forename: Miles R
authors.initials: MR
authors.lastname: Stanford
authors.forename: Philip I
authors.initials: PI
authors.lastname: Murray
authors.forename: Luke A
authors.initials: LA
authors.lastname: O'Neill
authors.forename: Graham R
authors.initials: GR
authors.lastname: Wallace
mesh_terms: D001528:Behcet Syndrome / Q000175:diagnosis / Q000235:genetics*; D004247:DNA / Q000032:analysis; D017789:Granuloma, Pyogenic / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007930:Leucine / Q000235:genetics; D008010:Lichen Planus / Q000175:diagnosis / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics* / Q000378:metabolism; D012694:Serine / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics
chemical_list: D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D012694:Serine; D004247:DNA; D007930:Leucine