Analyzing the relation between the variation (RS924080) of IL23R-IL12RB2 region and the expressions of IL23R and IL12RB2 genes identified in a Behçet's Disease-GWAS study.

Behçet's disease (BD) is an inflammatory disorder of unknown etiology characterized with recurrent inflammatory attacks and increased production of proinflammatory cytokines. A genome-wide association study (GWAS) identified an association between a polymorphism in the IL23R-IL12RB2 locus (rs924080) and Turkish BD patients by Remmers et al in 2010 (P < 0.0001), which was confirmed by Xavier et all in 2012. To delineate whether this particular polymorphism is associated with enhanced proinflammatory responses, IL-12 receptor β2 subunit (IL-12RB2), IL-23 receptor (IL-23R) expression and proinflammatory cytokine production were investigated in healthy individuals homozygous (AA) (n=4) or heterozygous for the risk A allele (AG) (n=6) or homozygous for the common G allele (GG) (n=4). Peripheral blood mononuclear cells (PBMC) were isolated and total RNA from PBMC was obtained and reverse-transcribed into cDNA. IL-12RB2 and IL-23R expression was assessed by real-time quantitative RT–PCR. Data analysis was performed using the Ct method, mRNA expression levels were compared by non-parametric Kruskal-Wallis test. IL-12RB2 and IL-23R expression levels and IL-12RB2 stimulation indices were comparable among different genotype groups. By contrast, IL-23R stimulation indices of AA and AG groups were significantly higher than the GG group (p=0.042). The AA genotype group's average stimulation index for IL-23R was greater than those of AG and GG groups. These results suggest that the rs924080 risk A allele does not affect the baseline expression levels of IL-12RB2, IL-23R, IFN- and TNF- but enhances the IL-23R and TNF- expression capacity in response to LPS stimulation. But also appears to enhance baseline IL-6 production. Based on the LPS stimulation results, it is tempting to speculate that individuals with the rs924080 A allele give exaggerated inflammatory responses to bacterial pathogens ultimately leading to BD development.