In contrast to the strong associations of the NOD2 SNPs rs2066844 (p=3.51 x 10(-3)), rs2066845 (p=1.54 x 10(-2)), and rs2066847 (p=1.61 x 10(-20)) with CD susceptibility, no significant association of rs72796353 with CD or UC susceptibility was found.
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.
Focusing on TNFSF15 instead ofNOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohn’s disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients.
In general, genes encoding cytokines are genetically polymorphic and polymorphisms in genes IL23R el IL17F were shown associated with susceptibility to Crohn's disease and ulcerative colitis which in their turn are considered as risk factors for developing colorectal cancer (CRC).
This study was performed in a group of patients with UC to test the possible role of IL23R SNPs in conferring susceptibility or protection against the disease.
Recent studies from India have reported an association with UC and a single polymorphism (SNP) in CARD15/NOD2 (SNP5, rs2066842), which has not been reported in Caucasian UC cohorts.
Three common NOD2 mutations are associated with Crohn's disease (p=5.08×10(-7), 1.67×10(-6), and 1.87×10(-2) for 1007fs, R720W, and G908R, respectively), but not with ulcerative colitis (p=0.1046, 0.1269, and 0.8929, respectively).
Moreover, genome-wide association studies have revealed that variants of the gene encoding the IL-23 receptor, as well as the locus harboring the gene encoding the p40 chain, confer genetic risk for developing Crohn's disease (CD) and ulcerative colitis (UC).
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.
Intriguingly, association with epithelial barrier genes seems specific to ulcerative colitis--the converse of NOD2 and the autophagy genes which are Crohn's-specific.
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.
IL-23R gene variants have been identified as risk factors for two major inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, but how they contribute to disease is poorly understood.
We now have a much more detailed appreciation of the molecular genetic architecture of inflammatory bowel disease (IBD), and particularly the areas of overlap between Crohn's disease (CD) and ulcerative colitis (UC) (such as Th17 pathways) and the pathways which are disease-specific (such as NOD2 and autophagy for CD and the MHC and epithelial barrier genes for UC).
Interleukin-23 is involved in pro-inflammatory signaling; genetic variation in the interleukin-23 receptor (IL23R) has been consistently associated with CD and UC risk.