title: IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis.
abstract: 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.
authors: Leukocyte Inflammation Research Laboratory, Department of Physiology, University of Otago, Dunedin, New Zealand.
authors: J
authors: J
authors: Hazlett
authors: L K
authors: LK
authors: Stamp
authors: T
authors: T
authors: Merriman
authors: J
authors: J
authors: Highton
authors: P A
authors: PA
authors: Hessian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics*; D007378:Interleukins / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: C515500:IL23R protein, human; D020381:Interleukin-17; D007378:Interleukins; D018123:Receptors, Interleukin; D018664:Interleukin-12; D002097:C-Reactive Protein; D000098546:Interleukin-21