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Background  The  IL23R  gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of  IL23R  variants.    Methods  Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10  IL23R  SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in  SLC22A4 /OCTN1 (1672 C→T) and  SLC22A5 /OCTN2 (–207 G→C).    Results  All  IL23R  gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [ P  = 1.92×10 −11 ; OR 1.56; 95 % CI (1.37–1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [ P  = 0.004; OR 4.24; CI (1.46–12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [ P  = 8.04×10 −8 ; OR 0.43; CI (0.31–0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the  IL23R  gene and the CD susceptibility genes  CARD15  and  SLC22A4/5 .    Conclusion    IL23R  is an IBD susceptibility gene, but has no epistatic interaction with  CARD15  and  SLC22A4/5 . rs1004819 is the major  IL23R  variant associated with CD in the German population, while the p.Arg381Gln  IL23R  variant is a protective marker for CD and UC.

rs1004819 Is the Main Disease-Associated IL23R Variant in German Crohn's Disease Patients: Combined Analysis of IL23R, CARD15, and OCTN1/2 Variants