title: 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.
authors.affiliation: Department of Medical Genetics, University of Pecs, Pecs, Hungary. noemi.polgar@aok.pte.hu
authors.forename: N
authors.initials: N
authors.lastname: Polgar
authors.forename: V
authors.initials: V
authors.lastname: Csongei
authors.forename: M
authors.initials: M
authors.lastname: Szabo
authors.forename: V
authors.initials: V
authors.lastname: Zambo
authors.forename: B I
authors.initials: BI
authors.lastname: Melegh
authors.forename: K
authors.initials: K
authors.lastname: Sumegi
authors.forename: G
authors.initials: G
authors.lastname: Nagy
authors.forename: Z
authors.initials: Z
authors.lastname: Tulassay
authors.forename: B
authors.initials: B
authors.lastname: Melegh
mesh_terms: D000328:Adult; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D006814:Hungary; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D053614:Janus Kinase 2 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D054399:Receptors, CCR6 / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics*
chemical_list: C106311:CCR6 protein, human; D054399:Receptors, CCR6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2