The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.
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.
Specifically the G149R, V362I, and R381QIL23Rα chain variants are linked to protection against the development of Crohn disease and ulcerative colitis in humans.
The aims of this study were to replicate the association of IL23R with Crohn's disease (CD), examine subphenotype relationships, and look for evidence of epistasis with the known CD susceptibility gene CARD15 and susceptibility haplotype IBD5 in a large collection of CD patients.
These observations suggest that IL23R makes a substantial contribution to CD susceptibility, larger than that estimated from the population frequency of the R381Q variant.
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.
There was no association between TNFSF15 or IL23R variants and UC in Korean individuals, in contrast to previous reports of a shared association of the IL23R gene with both CD and UC in Caucasian individuals.
The IL-22 levels in carriers of CD risk-increasing IL23R variants were significantly higher than in carriers of CD risk-decreasing IL23R variants (P = 0.008).
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.
The rare Q allele of IL23Rrs11209026 polymorphism was underrepresented in both paediatric and adult CD cases (P = 0.0018 and P = 0.04, respectively) and no difference was observed between the childhood and the adult cohort.
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 single nucleotide polymorphisms (SNPs) have been associated with several autoimmune diseases, including Crohn's disease and rheumatoid arthritis.
Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations.
Pooled OR and 95% CI was used to assess the association between the allelic, dominant and recessive models of IL23Rrs11209026 and rs10889677 polymorphisms and UC and CD risk.