Investigation of association of the IL12B and IL23R genes with psoriatic arthritis

Abstract

ObjectiveRecent reports have confirmed association of single-nucleotide polymorphisms (SNPs) mapping to the interleukin-23 receptor (IL-23R) and IL-12β genes with psoriasis susceptibility. The aim of this study was to determine whether these variants are also associated with susceptibility to psoriatic arthritis (PsA).MethodsTwo IL23R SNPs (rs7530511 and rs11209026) and 2 IL12B SNPs (rs3212227 and rs6887695) were genotyped in DNA samples from 520 white patients with PsA and 2,260 control subjects, all of whom resided in the UK. For SNP rs3212227, data on a larger group of controls (n = 4,681) were publicly available; this information was used in the analysis. Genotype counts were compared between patients with PsA and population controls, using the trend test.ResultsA haplotype comprising carriage of the common variants of both IL23R SNPs was associated with PsA susceptibility (adjusted P = 0.013 [1,000 permutations]). Both IL12B SNPs were independently associated with PsA susceptibility, and this association was strongest under a dominant model, with homozygosity for the common allele being more frequent in patients with PsA than in control subjects: for rs3212227, the odds ratio (OR) for carriage of AA versus other genotypes was 1.43 (95% confidence interval [95% CI] 1.17–1.76); for rs6887695, the OR for carriage of GG versus other genotypes was 1.43 (95% CI 1.18–1.74).ConclusionVariation within IL23R and IL12B is associated with susceptibility to both psoriasis and PsA. The effect sizes observed in patients with PsA appear to be smaller than those previously reported in patients with psoriasis, suggesting that both loci are primarily associated with psoriasis susceptibility. However, this does support the idea that the genetic etiology of the psoriasis present in patients with PsA has susceptibility loci in common with those observed in patients with uncomplicated psoriasis.

Variants in RUNX3 Contribute to Susceptibility to Psoriatic Arthritis, Exhibiting Further Common Ground With Ankylosing Spondylitis

“…Expression of RUNX3 in synovial tissue. Electrophoresis of conventional reverse transcription-polymerase chain reaction products shows expected amplicon sizes of products for the common product for RUNX3 isoforms (201 bp; lanes 2-11), GAPDH (316 bp; lanes [12][13][14][15][16][17][18][19][20][21], and the long isoform of RUNX3 (440 bp; lanes 23-32). Lanes 1 and 22, Size standard (pUC19); lanes 2, 12, and 23, leukocytes; lanes 3-10, 13-20, and 24-31, synovia; lanes 3-7, 13-17, and 24-28, synovia from osteoarthritis patients; lanes 8-10, 18-20, and 29-31, synovia from rheumatoid arthritis patients; lanes 11, 21, and 32, nontemplate control.…”

IL-17 and Its Receptor System: a New Target for Psoriatic Arthritis

“…The immunopathogenesis of psoriatic disease is complex and still evolving. In this complex milieu, pathogenic T cell subpopulations (T h 1, T h 17, T h 22) and their signature cytokines (IFN-γ, IL-1β, IL-6, TNF-α, IL-17, IL-22), chemokines, adhesion molecules, growth factors like nerve growth factor (NGF), and neuropeptides act in an integrated way through their corresponding receptors to evolve pathognomonic features of psoriasis and psoriatic arthritis [3,4,[16][17][18][19][20][21]. Cytokines are the primary products of immune activation.…”

“…The role of innate and adaptive immune responses is now well established in its pathogenesis. Psoriatic disease is strongly believed as a T cell-mediated autoimmune disease of the skin and joints based upon the following observations: (i) CD4 + T cell targeted immunotherapy clears active plaques of psoriasis [22]; (ii) transplanted nonlesional psoriatic skin converts to a psoriatic plaque subsequent to intradermal administration of T cells activated with an antigen cocktail in SCID mice [23]; (iii) blocking of the T cell co-stimulatory molecule improves psoriasis in the SCID mouse-psoriasis xenograft model [24]; (iv) T h 17 celldriven cytokines contribute to the pannus formation, osteoclast activation, and new bone formation in PsA [17][18][19][25][26][27].…”

“…A variety of genetic, immunologic, and environmental factors have been suggested to contribute to PsA pathogenesis [3,4,[14][15][16]. Single nucleotide polymorphisms in IL23A, IL23R, as well as TRAF3IP2 (Act1), a downstream target of the IL-17 receptor (IL-17R), confer susceptibility to PsA, implying a central role of the IL-23/IL-17 axis in PsA disease pathogenesis [17][18][19]. Considering the strong association of IL-17 and psoriatic disease, IL-17 targeted therapy for PsA has been developed and has shown promises in preclinical and clinical trials.…”

Genetic Factors in Immunopathogenesis of Psoriasis and Psoriatic Arthritis

“…Гомозигота по основному аллелю C/C поли-морфизма rs6887595 (IL12B) строго ассоциирова-на с субфенотипами ПсА [25]. Многочисленные исследовательские работы подтверждают ассо-циацию генов IL12B, IL23R с восприимчивостью к ПС и ПсА [18,19].…”