Il23r Gene Variants Influence Response Rate To Infliximab In Ulcerative Colitis

Several clinical and pathological features distinguish ulcerative colitis (UC) from Crohn's disease (CD).Whereas there have been more than 30 susceptibility loci identified for CD in recent genome-wide studies (GWAS), there is still a strong need for further identification of disease specific susceptibility loci in ulcerative colitis (UC).Most of the UC susceptibility genes reported so far have been found to be also involved in Crohn's disease, and the involved pathways can therefore be attributed to more general functions with its disturbance contributing to both subtypes of inflammatory bowel disease (IBD) Due to the lower relative sibling risk in UC (6-9) as compared with Crohn's disease (5-35), susceptibility genes in UC have indeed proven to be harder to detect than in Crohn's disease.We performed a genome-wide association analysis of 666,009 single nucleotide polymorphisms (SNP) using the Affymetrix® Genome-wide human SNP array 6.0 in 1043 UC patients and 1703 healthy controls of German origin.This panel A had 80% power to detect a variant with an odds ratio of 1.4 or higher at the 5% significance level, assuming a frequency of at least 10% of the disease-associated allele in healthy controls.According to the genomic inflation factor of λ(GC)=1.13genetic heterogeneity was low.Novel UC specific associations outside of previously reported regions, were visually inspected to exclude false positive associations and the 175 most strongly associated SNPs passing quality control were genotyped in additional panels of European descent totaling 3582 UC patients and 7131 healthy controls in the final combined analysis.Besides others, the strongest association signals were detected in regions on chromosome 22 and chromosome 7 with highly significant P-values (P=4.21E-08 and P=8.81E-11, respectively).Both loci encode biologically interesting candidates with regard to UC pathogenesis.