Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease

Am J Gastroenterol. 2009 Jul;104(7):1737-44. doi: 10.1038/ajg.2009.163. Epub 2009 May 19.


Objectives: Recently, a genome-wide association study showed that single-nucleotide polymorphisms (SNPs) in the chromosome 4q27 region containing IL2 and IL21 are associated with celiac disease. Given the increased prevalence of inflammatory bowel disease (IBD) among celiac disease patients, we investigated the possible involvement of these SNPs in IBD.

Methods: Five SNPs 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 a large German IBD cohort. The study population comprised a total of 2,948 Caucasian individuals, including 1,461 IBD patients (ulcerative colitis (UC): n=514, Crohn's disease (CD): n=947) and 1,487 healthy unrelated controls.

Results: Three of the five celiac disease risk markers had a protective effect on UC susceptibility, and this effect remained significant after correcting for multiple testing: rs6840978: P=0.0082, P(corr)=0.049, odds ratio (OR) 0.77, 95% confidence interval (CI) 0.63-0.93; rs6822844: P=0.0028, P(corr)=0.017, OR 0.73, 95% CI 0.59-0.90; rs13119723: P=0.0058, P(corr)=0.035, OR 0.75, 95% CI 0.61-0.92. A haplotype consisting of the six SNPs tested was markedly associated with UC susceptibility (P=0.0025, P(corr)=0.015, OR 0.72, 95% CI 0.58-0.89). Moreover, in UC, epistasis was observed between the IL23R SNP rs1004819 and three SNPs in the KIAA1109/TENR/IL2/IL21 block (rs13151961, rs13119723, and rs6822844).

Conclusions: Similar to other autoimmune diseases such as celiac disease, rheumatoid arthritis, type 1 diabetes, Graves' disease, and psoriatic arthritis, genetic variation in the chromosome 4q27 region predisposes to UC, suggesting a common genetic background for these diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Alleles
  • Case-Control Studies
  • Celiac Disease / epidemiology
  • Celiac Disease / genetics*
  • Celiac Disease / immunology
  • Chromosome Mapping
  • Colitis, Ulcerative / epidemiology
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / immunology
  • Confidence Intervals
  • Epistasis, Genetic*
  • Female
  • Genetic Linkage
  • Genetic Markers / genetics*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Incidence
  • Interleukin-2 / genetics
  • Interleukins / genetics
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Probability
  • Receptors, Interleukin / genetics
  • Risk Factors
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Sex Distribution


  • Genetic Markers
  • IL23R protein, human
  • Interleukin-2
  • Interleukins
  • Receptors, Interleukin
  • interleukin-21