title: Multiplex screening of 22 single-nucleotide polymorphisms in 7 Toll-like receptors: an association study in rheumatoid arthritis.
abstract: OBJECTIVE
  Toll-like receptors (TLR) have been implicated in the pathogenesis of arthritis. We investigated the role of functional variants of TLR in the disease phenotype and severity of rheumatoid arthritis (RA).
  
  
  METHODS
  All patients from a longterm observational inception cohort (n = 319) were genotyped for 22 single-nucleotide polymorphisms (SNP) in TLR2, 3, 4, 5, 7, 8, and 9 using multiplex assays. Clinical characteristics including sex, age at disease onset, rheumatoid factor (RF), and shared epitope positivity and disease activity score and radiological progression were taken into account. Genotypes were analyzed for association with Disease Activity Scores (DAS28) and joint damage (Rau scores) at 3 and 6 years.
  
  
  RESULTS
  After Bonferroni correction, there was a moderate association between RF positivity and TLR8-rs5741883. No other TLR variant was significantly associated with any RA clinical characteristics.
  
  
  CONCLUSIONS
  Using a large inception cohort and strict statistical evaluation, we could not identify an association between functional TLR variants and RA phenotype and disease severity. This suggests the functional TLR variants do not play a major role in RA phenotype and disease severity.
authors.affiliation: Institute for Inflammation Research, National University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Enevold
authors.forename: Timothy R D
authors.initials: TR
authors.lastname: Radstake
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Coenen
authors.forename: Jaap
authors.initials: J
authors.lastname: Fransen
authors.forename: Erik J M
authors.initials: EJ
authors.lastname: Toonen
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
mesh_terms: D017668:Age of Onset; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics*; D001175:Arthrography; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: D051193:Toll-Like Receptors