title: No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis.
abstract: BACKGROUND
  The objective was to study the potential genetic contribution of Toll-like receptor (TLR) genes in rheumatoid arthritis (RA). TLRs bind to pathogen-associated molecular patterns, and TLR genes influence both proinflammatory cytokine production and autoimmune responses. Host-pathogen interactions are involved in RA physiopathology.
  
  
  METHODS
  We tested SNPs of five TLR genes (TLR9, TLR2, TLR6, TLR1, and TLR4) in a cohort of 100 French families with RA. Genotypes were analyzed using the transmission disequilibrium test. As TLR2, TLR6, and TLR1 are located on chromosome 4, we determined the haplotype relative risk. Analyses were performed in subgroups defined by status for rheumatoid factor, anti-cyclic citrullinated peptide autoantibodies, and erosions.
  
  
  RESULTS
  We found no disequilibrium in allele transmission for any of the SNPs of the five TLR genes. In subgroup analyses, no associations were detected linking TLR9, TLR2, or TLR9/TLR2 to rheumatoid factor, anti-cyclic citrullinated peptide autoantibodies, or erosions. Haplotype analysis of the polymorphisms showed no haplotype associations in any of the subgroups.
  
  
  CONCLUSIONS
  We found no evidence of major effects of TLR gene polymorphisms in RA, although we tested different TLR phenotypes. Moreover, no associations were noted with autoantibody production or erosions.
authors.affiliation: EA-4222, University of Paris 13, Bobigny Cedex, Paris, France. olivier.jaen@club-internet.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Jaen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petit-Teixeira
authors.forename: Holger
authors.initials: H
authors.lastname: Kirsten
authors.forename: Peter
authors.initials: P
authors.lastname: Ahnert
authors.forename: Luca
authors.initials: L
authors.lastname: Semerano
authors.forename: Céline
authors.initials: C
authors.lastname: Pierlot
authors.forename: Francois
authors.initials: F
authors.lastname: Cornelis
authors.forename: Marie-Christophe
authors.initials: MC
authors.lastname: Boissier
authors.forename: Geraldine
authors.initials: G
authors.lastname: Falgarone
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: D051193:Toll-Like Receptors