MedWire News: German researchers have found that genetic variations in the chromosome 4q27 region predispose to ulcerative colitis (UC), in common with other autoimmune diseases such as celiac disease, rheumatoid arthritis, and Type 1 diabetes.
Stephan Brand from University Hospital, Munich, and colleagues therefore suggest there may be a common genetic background for these diseases.
A recent study showed that single-nucleotide polymorphisms (SNPs) in the chromosome 4q27 region containing the interleukin (IL) genes IL2 and IL21 are associated with celiac disease.
Given the increased prevalence of inflammatory bowel disease (IBD) among celiac-disease patients, the team investigated the possible involvement of these SNPs in IBD.
Five SNPs that were strongly associated with celiac disease within the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block on chromosome 4q27 and one coding SNP within the IL21 gene were analyzed in 2948 German Caucasian individuals.
These included 1461 IBD patients, of whom 514 had UC and 947 Crohn’s disease, and 1487 healthy, unrelated control individuals.
Three of the five celiac disease risk markers, the SNPs rs6840978, rs6822844, and rs13119723, were associated with a protective effect in UC susceptibility.
A haplotype consisting of six SNPs in the chromosome 4q27 region was associated with UC susceptibility, with an odds ratio of 0.72.
In UC, epistasis was observed between the IL23R SNP rs1004819 and three SNPs - rs13151961, rs13119723, and rs6822844 - in the IL2/IL21-containing chromosome 4q27 region.
The findings implicate IL-21, which is a major cytokine involved in Th17 cell differentiation, in the pathogenesis of UC, say the researchers in the American Journal of Gastroenterology.
They suggest that “certain treatment strategies directed against Th17 cells such as anti-IL23 antibodies, which were successfully applied in CD, may also be effective in UC.”
The team adds: “Our findings indicate a potential role for the chromosome 4q27 region as a general autoimmune risk locus.”
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