Interleukin 23 receptor gene polymorphisms and their role in the inflammatory status of rheumatoid arthritis patients in an Iranian population.

Abstract

Several investigations have disclosed the involvement of the interleukin (IL)-23/IL-17 pathway in rheumatoid arthritis (RA) pathogenesis. Here we investigated the association of single nucleotide polymorphisms (SNPs) in the IL23 receptor (IL23R) gene with RA risk. In addition, the role of these SNPs with the inflammatory state of the patients were determined. In this case-control study, 200 RA cases and 200 healthy subjects were recruited. Using allelic discrimination real-time polymerase chain reaction, both IL23R rs10489629 and rs1004819 SNPs were genotyped. The messenger RNA (mRNA) expression levels of IL-23R, IL-23, and IL-17A were determined in peripheral blood mononuclear cells (PBMCs). The serum levels of IL-23 and IL-17A were also determined. The A allele (odds ratio [OR]=1.52, 95% CI: 1.15-2.01; P= .0030), AA genotype (OR=2.41, 95% CI: 1.33-4.35; P= .0035), and AG genotype (OR=2.55, 95% CI: 1.56-4.16, P= .0002) of rs1004819 SNP was significantly associated with increased RA risk. The mRNA expression of IL-17A (fold change=2.55, P= .00027), IL-23 (fold change=1.62, P= .0081), and IL-23R (fold change=1.59, P= .0077) was significantly upregulated in the PBMCs from RA patients compared to that of healthy controls. Serum levels of IL-17A (P= .00019) and IL-23 (P= .00055) was significantly higher in the RA patients compared to the controls. No significant association was detected between patient data and SNPs. The IL-23/IL-27 pathway plays a role in RA pathogenesis, but IL23R gene rs1004819 SNP might not be regulating this pathway in RA disease.