The originally described association of IBD with STAT3 polymorphisms is corroborated for the two clinical phenotypes, CD and UC, in an independent population.
By contrast, variation in the gene encoding the interleukin-23 (IL-23) receptor subunit, as well as in the IL12B, STAT3 and NKX2-3 gene regions, is associated with both Crohn's disease and ulcerative colitis.
Our data confirm the association between JAK2 rs10758669 (p = 0.026, OR = 1.25, 95% CI = 1.04-1.50) and STAT3rs744166 (p = 0.04, OR = 0.83, 95% CI = 0.688-0.998) with CD, but not UC.
Logistic regression model was used to examine the association between single nucleotide polymorphism (SNP) of STAT3 and CD risk; the odds ratio (OR) and 95 % confident interval (95 % CI) were calculated.
Colonic expression of genes regulating STAT3 signaling and leukocyte recruitment and function was measured in pediatric patients with Crohn disease (CD) stratified by STAT3 genotype.
We confirmed associations of Crohn's disease with variants in MHC (rs7765379, P = 2.11 × 10(-59)), TNFSF15 (rs6478106, P = 3.87 × 10(-45)), and STAT3 (rs9891119, P = 2.24 × 10(-14)).
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).
Genome-wide association studies indicate that IL23R and five additional genes involved in Th17 differentiation (IL12B, JAK2, STAT3, CCR6 and TNFSF15) are associated with susceptibility to Crohn's disease and partly also to ulcerative colitis.
DNA was tested for three CD-associated NOD2 variants (3020insC, G908R, R702W), variants in IRGM, ATG16L1, IL12B, IL23R, STAT3, and a TLR5-stop mutation.
The results indicated that the STAT3rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11-1.30, I2 = 0%, Punadjusted<0.00001, PBonferroni<0.00005, PFDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08-1.36, I2 = 1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125).
This is the first study of the single marker association of IL23R, JAK2, and STAT3 polymorphisms with ulcerative colitis and Crohn's disease in a Turkish population.
Allelic association analysis (two-tailed) showed that three of the five targeted SNPs were significantly associated with overall susceptibility for CD (ZNF365, r10995271, P = 0.001; PTPN2, rs1893217, P = 0.005; STAT3, rs744166, P = 0.01).
The protective haplotype for MS in STAT3 is a risk allele for Crohn disease, implying that STAT3 represents a shared risk locus for at least two autoimmune diseases.
IL-6/STAT3/SOCS3 signaling pathway plays an important role in the pathogenesis of Crohn's disease by induction of the antiapoptotic factors Bcl-2 and Bcl-xl in lamina propria mononuclear cells (LPMCs).