title: The role of toll-like receptor variants in acute anterior uveitis.
abstract: OBJECTIVE
  Acute anterior uveitis (AAU) is the most common form of uveitis; however, while it is presumed to have an immunological basis, the precise underlying etiology remains elusive. Toll-like receptors (TLRs) have a key role in linking innate and adaptive immunity, thereby forming a molecular bridge between microbial triggers and the development of AAU. The purpose of this study was to investigate the role of TLR2 and TLR4 gene polymorphisms in the pathogenesis of AAU.
  
  
  METHODS
  The study comprised 225 confirmed cases of idiopathic or human leukocyte antigen (HLA) B27 (subtypes B*2701-2759; HLA-B27)-related AAU and 2,534 population-based controls from the Blue Mountains Eye Study. All participants were of Anglo-Celtic descent. Blood samples were collected for DNA extraction and genotyping. A total of 16 single nucleotide polymorphisms (SNPs) were selected for analysis and either directly genotyped or imputed to cover the common variations within the TLR genes. Data were analyzed at the allelic, genotypic and haplotypic levels.
  
  
  RESULTS
  Control subjects were significantly older than case subjects (p<0.0001). There was no significant difference in the gender composition between the case and control cohorts (p=0.18). One TLR2 SNP (rs11938228) was found to be associated with AAU at the allelic level (OR=1.28; p=0.017); however this association did not remain following adjustment for age and sex (p=0.067). None of the SNPs at the TLR4 locus were found to differ significantly between cases or controls, irrespective of adjustment for age and gender.
  
  
  CONCLUSIONS
  This study has confirmed that common TLR variants of moderate effect size do not predispose to AAU, undermining the implication of reported mutations in the selective perturbations of TLR expression and function evident in AAU.
authors: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
authors: Divya S
authors: DS
authors: Pratap
authors: Lyndell L
authors: LL
authors: Lim
authors: Jie Jin
authors: JJ
authors: Wang
authors: David A
authors: DA
authors: Mackey
authors: Lisa S
authors: LS
authors: Kearns
authors: Richard J
authors: RJ
authors: Stawell
authors: Kathryn P
authors: KP
authors: Burdon
authors: Paul
authors: P
authors: Mitchell
authors: Jamie E
authors: JE
authors: Craig
authors: Anthony J
authors: AJ
authors: Hall
authors: Alex W
authors: AW
authors: Hewitt
mesh_terms: D000208:Acute Disease; D000368:Aged; D000483:Alleles; D001315:Australia / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology; D014606:Uveitis, Anterior / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D044465:White People
chemical_list: D015796:HLA-B27 Antigen; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4