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.
Th17 T<sub>EM</sub> cells (expressing <i>IL17A, IL17F, RORC</i>, and <i>STAT3</i>) displayed a higher pathogenic/cytotoxic (<i>IL23R, IL18RAP</i>, and <i>GZMB, CD160, PRF1</i>) gene signature in CD relative to UC, while non-pathogenic/regulatory genes (<i>IL9, FOXP3, CTLA4</i>) were more elevated in UC.
IL23R was associated with CD and UC only in the absence of CARD15 mutations, whereas ATG16L1 was associated with CD in the presence and absence of CARD15 mutations.
We investigated associations with disease susceptibility, phenotype, and evidence for epistasis with CARD15 in 679 patients with Crohn's disease (CD) or ulcerative colitis (UC).
The data suggest that IBD1 may also contribute to susceptibility to ulcerative colitis, and that it is likely to be located in the 12 cM interval between D16S419 and D16S409.
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.
In contrast, PAB and GAB antibodies were not associated with NOD2/CARD15 or TLR4, response to medical therapy, or need for surgery.No associations were found in UC.
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.