IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis

Genes Immun. 2012 Apr;13(3):282-7. doi: 10.1038/gene.2011.80. Epub 2011 Dec 1.


The interleukin (IL)-17/IL-23 axis is an important pro-inflammatory pathway in rheumatoid arthritis (RA). IL-23 maintains CD4(+) T-helper 17 (Th(17)) cells, whereas IL-12 negates IL-17A production by promoting Th(1)-cell differentiation. We sought evidence for any effect of polymorphisms within the interleukin-23 receptor (IL-23R), IL-12 or IL-21 genes on serum cytokine concentrations in 81 patients with RA. Serum cytokines were measured using bead-based multiplex assays. Targeted cytokines were detected in up to 66% of samples. A subgroup of 48 patients had detectable serum IL-17A. Within this subgroup, patients, homozygous for the IL-23R rs11209026 major allele had significantly higher serum IL-17A concentrations compared with patients with the minor allele (394.51 ± 529.72 pg ml(-1) vs 176.11 ± 277.32 pg ml(-1); P = 0.017). There was no significant difference in any of the cytokine concentrations examined in patients positive for the minor allele vs homozygosity for the major allele of IL-12B rs3213337, IL-12Bpro rs17860508 and IL-21 rs6822844. Our results suggest the IL-23R Arg381Gln substitution may influence serum IL-17A concentrations. In patients with the 381Gln allele higher IL-23 concentrations may be needed to produce similar IL-17A concentrations to those in patients with the 381Arg allele. This suggests altered IL-23R function in patients with the minor allele and warrants further functional studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism
  • Female
  • Genotype
  • Humans
  • Interleukin-12 / blood
  • Interleukin-12 / genetics
  • Interleukin-17 / blood
  • Interleukin-17 / genetics*
  • Interleukins / blood
  • Interleukins / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin / genetics*
  • Young Adult


  • IL23R protein, human
  • Interleukin-17
  • Interleukins
  • Receptors, Interleukin
  • Interleukin-12
  • C-Reactive Protein
  • interleukin-21