IL23R-Protective Coding Variant Promotes Beneficial Bacteria and Diversity in the Ileal Microbiome in Healthy Individuals Without Inflammatory Bowel Disease.
In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10<sup>-6</sup>): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC.
Through mounting genetic investigations, it has been established that IL12B and IL23R gene single nucleotide polymorphisms have significant associations with autoimmune diseases including inflammatory bowel disease, psoriasis, and ankylosing spondylitis.
Mutations in the Interleukin (IL)-23/IL-23 receptor loci are associated with increased inflammatory bowel disease (IBD) susceptibility, and IL-23 neutralization has shown efficacy in early clinical trials.
IL23R (Interleukin 23 Receptor) Variants Protective against Inflammatory Bowel Diseases (IBD) Display Loss of Function due to Impaired Protein Stability and Intracellular Trafficking.
We genotyped three nonsynonymous IL-23R SNPs with amino acid changes (rs11209026, p.Arg381Gln; rs41313262rs41313262" genes_norm="149233">p.Val362Ile and rs11465797rs11465797" genes_norm="149233">p.Thr175Asn) in 198 patients with IBD (124 UC and 74 CD) and 100 healthy controls.
Interestingly, a functional single nucleotide polymorphism (SNP) in the IL-23 receptor gene (IL-23R; rs11209026, 1142 G wild-type A reduced function, Arg381Gln, rs11209026" genes_norm="149233">R381Q) seems to confer a measure of protection against development of inflammatory bowel disease (IBD; Crohn's disease, ulcerative colitis), ankylosing spondylitis, rheumatoid arthritis, psoriasis, thyroiditis, recurrent spontaneous abortion and asthma, suggesting that a perturbation in the IL-23 signaling pathway is likely to be relevant to the pathophysiology of these diseases.
Serum IL-17C levels are modified by IL23R genotypes and IL-17C mRNA correlates (r>0.5, P<0.001) with IL-17A, tumor necrosis factor (TNF)-α, C-C motif chemokine ligand 20 (CCL20) and IL-23 mRNA in the inflamed colon of IBD patients.
Additional suggestive associations (P < 4.2 × 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994.
Some IBD associated genes are involved in innate immunity, in the autophagy and in the inflammatory response such as NOD2, ATG16L1 and IL23R, while other are implicated in immune mediated disease (STAT3) and in susceptibility to mycobacterium infection (IL12B).
Variants of IL23R gene were investigated for association with many diseases like chronic inflammatory disorders, RA, inflammatory bowel diseases and the susceptibility to the development of gastric cancer but no data are available concerning the association of IL23R gene (rs11209026) polymorphism with HCC development in HCV patients.
The subunit of IL-23 (IL12B) and its receptor (IL23R) gene single-nucleotide polymorphisms (SNPs) have been shown to be associated with several autoimmune diseases such as inflammatory bowel disease, psoriasis and ankylosing spondylitis.
After Bonferroni correction for multiple testing, both the homozygous and the heterozygous variant genotypes of IL23R G>A(rs11209026) (OR(CD,adj): 0.38, 95% CI: 0.21-0.67, p = 0.03; OR(IBD,adj) 0.43, 95% CI: 0.28-0.67, p = 0.007) and PTPN22 1858 G>A(rs2476601) (OR(CD,unadj) 0.54, 95% CI: 0.41-0.72, p = 7*10-4; OR(IBD,unadj): 0.61, 95% CI: 0.48-0.77, p = 0.001) were associated with reduced risk of CD.
Three risk loci shared with ankylosing spondylitis and psoriasis (the MHC class I region, ERAP1 and IL23R and the MHC class I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and Behçet's disease.
Three risk loci shared with ankylosing spondylitis and psoriasis (the MHC class I region, ERAP1 and IL23R and the MHC class I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and Behçet's disease.
In this study, we investigated the mRNA and protein levels of IL-12p40, tumor necrosis factor-like cytokine 1A (TL1A), Janus kinase 2 (JAK2), and IL-23R both locally and systemically in Chinese IBD patients.