This deficit is independent of concurrent active inflammation and cannot be seen in active small intestinal ulcerative colitis (UC; pouchitis) as well as NOD2 wild-type graft vs. host ileitis.
In addition to the IL2/IL21 locus, we observed association of the TT genotype of SNP rs1545620 in MYO9B with UC (P = 0.0169; OR = 0.29, 95% CI 0.11-0.78) and association of rs17375018 in IL23R with pancolitis in Chinese UC patients (P = 0.002; OR = 2.38, 95% CI 1.41-4.02).
The data show an association of both IL23R SNPs with overall IBD (statistically stronger, rs7517847; odds ratio [OR] = 0.79, 95% confidence interval [CI]: 0.67-0.94, minor allele frequencies: 0.355 in IBD patients versus 0.410 in controls; P = 0.005), somewhat stronger in Crohn's disease (OR = 0.74, 95% CI: 0.61-0.91) than in ulcerative colitis (OR = 0.84, 95% CI: 0.69-1.03).
Here, we report the mutational analyses of CARD15 in 453 patients with CD, including 166 sporadic and 287 familial cases, 159 patients with ulcerative colitis (UC), and 103 healthy control subjects.
NOD2 gene 3020insC frameshift mutation is not a major contributor to the susceptibility to both Crohn's disease and ulcerative colitis in Chinese Han patients.
One hundred and eighty unrelated IBD patients [57 Crohn's disease (CD) and 123 ulcerative colitis (UC)] and 186 healthy controls were genotyped for the following known genetic susceptibility variants: NOD2 - Arg702Trp (rs2066844), rs2066845" genes_norm="64127">Gly908Arg (rs2066845) and Leu1007insC (rs2066847), as well as IL23R - rs11209026;rs901312933" genes_norm="149233;55054">Arg381Gln (rs11209026) and ATG16L1 - rs2241880;s2241880;rs1384936174" genes_norm="55054;64127">Thr300Ala (rs2241880).
Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis.
Crohn's disease, but not ulcerative colitis, is associated with genetic variation in NOD2 and an autophagy gene, ATG16L1, both of which affect the intracellular processing of bacterial components.
Polymorphisms of NOD2 (R702W, G908R and L1007fs) and TLR4 (Asp299Gly and Thr399Ile) genes were analyzed in 106 patients with IBD (68 with ulcerative colitis [UC], 38 with Crohn's disease [CD]) and 160 healthy controls using polymerase chain reaction-restriction fragment length polymorphism.
We were able to replicate the association of the IL23R variants with CD as well as HLA-DRB1*0103 with UC; confirmation of TNFRSF1A association with UC needs additional studies.
The presence of NOD2 allelic variants was primarily associated with fibrostenosis, secondarily with small bowel disease and small bowel surgery, and was inversely associated with UC-like disease.
The polymorphisms TLR2 (rs1816702), NFKB1 (rs28362491), TNFRSF1A (rs4149570), IL6R (rs4537545), IL23R (rs11209026) and PTPN22 (rs2476601) were associated with risk of CD and the polymorphisms TLR2 (rs1816702), TLR4 (rs1554973 and rs12377632), TLR9 (rs352139), LY96 (rs11465996), NFKBIA (rs696), TNFA (rs1800629), TNFRSF1A (rs4149570), IL10 (rs3024505), IL23R (rs11209026), PTPN22 (rs2476601) and PPARG (rs1801282) were associated with risk of UC.
Forty-four percent of patients with CD were positive for >or=1 mutant allele of NOD2/CARD15 compared to 2% of UC patients (p < 0.001) and 19% of healthy twins (p= 0.02).
The study indicates that IL23R-rs11805303 and PTPN2-rs2542151 might contribute to the development of UC and NOD2-P268S might be involved in the etiology of CD in the Chinese Han population.
To investigate the contribution of three polymorphisms of MYO9B gene for predisposition to Crohn's disease and ulcerative colitis, their association with clinical phenotypes, particularly intestinal permeability, and possible interaction with the CARD15 gene.
Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease.