Genetic variants in toll-like receptors are not associated with rheumatoid arthritis susceptibility or anti-tumour necrosis factor treatment outcome

PLoS One. 2010 Dec 15;5(12):e14326. doi: 10.1371/journal.pone.0014326.

Abstract

Background: Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication.

Methodology and principal findings: 22 single nucleotide polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort consisting of 378 RA patients and 294 controls. Significantly associated variants were investigated in replication cohorts from The Netherlands, United Kingdom and Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were treated with anti-TNF medication. Using these patients and a replication cohort (269 Swedish patients) we analysed if genetic variants in TLR genes were associated with anti-TNF outcome. In the discovery phase of the study we found a significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA disease susceptibility. Meta-analysis of discovery and replication cohorts did not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF outcome in the Dutch but not in the Swedish population.

Conclusion: We conclude that genetic variants in TLRs do not play a major role in susceptibility for developing RA nor in anti-TNF treatment outcome in a Caucasian population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Netherlands
  • Polymorphism, Single Nucleotide
  • Sweden
  • Toll-Like Receptor 5 / genetics*
  • Toll-Like Receptor 7 / genetics*
  • Toll-Like Receptors / genetics*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism*
  • United Kingdom

Substances

  • TLR5 protein, human
  • TLR7 protein, human
  • Toll-Like Receptor 5
  • Toll-Like Receptor 7
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha