rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants.

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 = 1.92x10(-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 = 8.04x10(-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. 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.