Genetic polymorphisms of IL-23R and IL-17A and novel insights into their associations with inflammatory bowel disease

Abstract

The results provide insights into the genetic and epigenetic interactions in the IL-23R/IL-17 axis that are associated with elevated expression of IL-17 and IBD pathogenesis.

Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet's disease in Korean population

“…Interestingly, the IL17A gene and the HLA B51, TNFα, and SUMO4 genes that are known to increase the BD risk are located on the same chromosome (chromosome 6), suggesting an association between IL17A variants and disease susceptibility (Hou et al, 2008;Remmers et al, 2010;Verity et al, 1999). As the evidence of IL17A genetic variants having a potential risk of the autoimmune disease development, our very recent study investigating the association of genetic variants of IL23R and IL17A with inflammatory bowel disease identified the relationship of rs2275913 of IL17A with the risk of UC (Kim et al, 2011). Although we were not able to find any association of SNPs of STAT4 with the risk of intestinal BD in the individual polymorphism analysis, they were found to exert a significant synergistic effect both with IL17A and IL23R in gene-gene interaction analysis.…”

“…Polymorphism rs8193036 of IL17A may give a significant influence on binding affinity of transcription factors. We previously reported that rs8193036 of IL17A was significantly related to a higher level of IL-17A mRNA expression in patients with inflammatory bowel disease and showed a substantial activity to transcription factor complexes as a kind of regulatory mechanism (Kim et al, 2011). Notably, the joint effects of these two SNPs (IL17A and IL23R) raised the risk of intestinal BD as the number of risk genotypes increased.…”

Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

“…IL-23R and IL-17A variants have been linked to both UC and CD in a part of the Korean population, and a significant polymorphism in the promoter region of IL-17A has been identified (123). Other susceptibility genes involved in the IL-23 pathway, such as IL-12B, JAK2, and STAT3, have also been associated with CD (280).…”

Targeting Interleukins for the Treatment of Inflammatory Bowel Disease—What Lies Beyond Anti-TNF Therapy?

“…[121][122][123][124] Preclinical models have shown that blocking IL-12 in vivo ameliorated TNBS colitis. 125 Genome wide association studies identified polymorphisms in the IL-23 receptor gene as an important genetic determinant of IBD risk 126,127 and genetic variation in the p40 molecule itself also has been associated with IBD susceptibility. 128 In the clinical arena, an initial phase II trial several years ago enrolling around 100 patients did not show a persistent benefit with 3 mg of ustekinumab for moderateto-severe CD, despite an initial improved clinical response at 6 weeks.…”