Jürgen Glas 1 , 2 , Julia Seiderer 1 , Martin Wetzke 1 , 2 , Astrid Konrad 1 , Helga-Paula Török 1 , Silke Schmechel 1 , Laurian Tonenchi 2 , Christine Grassl 2 , Julia Dambacher 1 , Simone Pfennig 1 , Kerstin Maier 2 , Thomas Griga 4 , Wolfram Klein 5 , Jörg T. Epplen 5 , Uwe Schiemann 6 , Christian Folwaczny 3 , Peter Lohse 7 , Burkhard Göke 1 , Thomas Ochsenkühn 1 , Bertram Müller-Myhsok 8 , Matthias Folwaczny 2 , Thomas Mussack 3 , Stephan Brand 1 , *
5 September 2007
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.
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).
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.