Z Gastroenterol 2008; 46 - P039
DOI: 10.1055/s-0028-1089415

Novel protective markers for ulcerative colitis in the IL2/IL21 region suggest a common genetic background for ulcerative colitis and celiac disease

J Glas 1, M Wetzke 2, D Roeske 3, S Pfennig 1, W Klein 4, JT Epplen 4, T Griga 5, U Schiemann 6, B Göke 1, T Ochsenkühn 1, M Folwaczny 7, B Müller-Myhsok 3, S Brand 1
  • 1Klinikum der Universität München, Medizinische Klinik II, München, Germany
  • 2Medizinische Hochschule Hannover, München, Germany
  • 3Max-Planck-Institut für Psychiatrie, München, Germany
  • 4Ruhr-Universität, Bochum, Germany
  • 5Knappschaftskrankenhaus, Dortmund, Germany
  • 6Inselspital, Bern, Switzerland
  • 7Klinikum der Universität München, München, Germany

Background/Aim: To analyze whether recently identified genetic risk markers for celiac disease influence the susceptibility to inflammatory bowel disease (IBD), we tested five single nucleotide polymorphisms (SNPs) associated with celiac disease in the 4q27 region (rs6840978, rs6822844, rs12642902, rs13119723, rs13151961) and the coding SNP rs4833837=p.Cys78Cys within the IL21 gene for association with IBD in a large German IBD cohort.

Methods: The six SNPs were genotyped in a total of 2948 Caucasian individuals comprising 1461 IBD patients (514 with ulcerative colitis, 947 with Crohn's disease) and 1487 healthy unrelated controls performing a case-control association study.

Results: Four of the five SNPs, which showed the most significant associations with celiac disease in a recent genome-wide association study (GWA), were strongly associated with ulcerative colitis in the German population (rs6840978, p=0.0081, OR 0.77, 95% CI 0.63–0.94; rs6822844, p=0.0028, OR 0.73, CI 0.59–0.90; rs13119723, p=0.0058, OR 0.75, CI 0.61–0.93 and rs13151961, p=0.0138, OR 0.77, CI 0.62–0.95). Suggestive association with ulcerative colitis was observed for the fifth SNP (rs12642902, p=0.0669, OR 0.86, CI 0.73–1.01). For three of the four SNPs associated with ulcerative colitis, we further revealed a trend towards association with Crohn's disease (rs6822844, p=0.0601, OR 0.85, CI 0.72–1.01; rs13119723, p=0.0817, OR 0.87, CI 0.74–1.02 and rs13151961, p=0.0801, OR 0.86, CI 0.73–1.02). Similar to the GWA analyzing celiac disease, for all SNPs analyzed, the minor allele was less frequent in the case group compared to the control group suggesting a protective effect of these genetic variants against IBD. For both ulcerative colitis and Crohn's disease, there were no significant differences between cases and controls regarding the allele frequencies of rs4833837 (p.Cys78Cys).

Conclusion: These results indicate that SNPs in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block do not only influence susceptibility to celiac disease but also to ulcerative colitis suggesting that these two diseases may share a common genetic background.