Investigation of JAK2, STAT3 and CCR6 polymorphisms and their gene–gene interactions in inflammatory bowel disease

Abstract

Genome-wide association studies identified many loci associated with the two forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). Components of the interleukin-23 signalling pathway, such as IL23R, JAK2 and STAT3, have been implicated in both diseases. In addition, emerging evidence supports the role of IL23-driven Th17 cells in inflammation. Here, we studied the susceptibility nature of three components of IL23 signalling and Th17 cell differentiation: JAK2 rs10758669, STAT3 rs744166 and CCR6 rs2301436 initially associated with CD in Hungarian CD and UC patients. A total of 616 unrelated subjects with either form of IBD and 496 healthy controls were genotyped with PCR-RFLP methods. We also tested the genetic interactions of JAK2, STAT3 and CCR6 polymorphisms in a pairwise fashion with regard to disease risk. We could confirm the susceptibility of STAT3 rs744166 TT homozygotes for UC (OR: 1.483, 95% CI: 1.103-1.992, P = 0.009). Data on genetic interaction reveals that the above JAK2 and STAT3 risk alleles contribute to CD susceptibility in combination with each other (OR: 2.218; 95% CI: 1.097-4.487; P = 0.024), while the JAK2 variant shows a tendency to confer UC risk only on a wild-type STAT3 background (OR: 1.997, 95%CI: 0.994-4.009, P = 0.049). Our results may help in understanding how these natural variants contribute to development of IBD through their genetic association.

Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene–gene interactions in Crohn’s disease and ulcerative colitis in a Turkish population

“…It is thought that the IL23/IL23R signal pathway may play a central role in the pathogenesis of IBD. Though there are studies showing that IL23R, JAK2, and STAT3 cause susceptibility to UC and CD in different ethnic groups, the results are not consistent (6,13,(15)(16)(17)(18)(19)(20)(21). The reason for this discrepancy may be that IBD in different ethnic communities may appear through different predominant mechanisms.…”

Identification of possible pathogenic pathways in Behçet’s disease using genome-wide association study data from two different populations

“…The genes such as JAK2 and STAT3 in the IL23 signaling pathway contribute to a surprising range of autoimmune diseases, including BD and inflammatory bowel disease. [53][54][55] As part of this pathway, low-frequency and rare variants in the FN3, fibronectin tenth type III domain of IL23R gene were detected by targeted resequencing of TR and JP samples. 40 As shown in Table 2, IL2RB gene, which has the same FN3 domain, is targeted by the SNPs in both TR and JP populations.…”

The polymorphism and gene expression of chemokine receptor 6 is associated with digestive disorders in rabbits

“…Our case-control study, we finally found that T allele, TC/TT genotypes can significantly reduce susceptibility to digestive disorders in rabbit. Similarly, Polgar et al (2012) reported that the polymorphisms of CCR6 gene is associated with IBD in human. However, studies relating to CCR6 gene in farm animals are very scarce, thus, no comparisons could be made with other research in farm animals.…”

“…Subsequently genome-wide association studies have identified that CCR6 gene is a susceptibility loci for Crohn's disease patients (Barrett et al, 2008). In addition, Polgar et al (2012) reported that the rs2301436 of CCR6 gene is associated with IBD in human (Hungarian population). However, to our knowledge, the information of CCR6 gene polymorphisms and its association with digestive disorders in farm animals is limited.…”