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

Publication

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

Journal Paper/Review - Sep 5, 2007

Glas Jürgen, Epplen Jörg T, Schiemann Uwe, Folwaczny Christian, Lohse Peter, Göke Burkhard, Ochsenkühn Thomas, Müller-Myhsok Bertram, Folwaczny Matthias, Mussack Thomas, Klein Wolfram, Griga Thomas, Maier Kerstin, Seiderer Julia, Wetzke Martin, Konrad Astrid, Török Helga-Paula, Schmechel Silke, Tonenchi Laurian, Grassl Christine, Dambacher Julia, Pfennig Simone, Brand Stephan

Citation

Glas J, Epplen J, Schiemann U, Folwaczny C, Lohse P, Göke B, Ochsenkühn T, Müller-Myhsok B, Folwaczny M, Mussack T, Klein W, Griga T, Maier K, Seiderer J, Wetzke M, Konrad A, Török H, Schmechel S, Tonenchi L, Grassl C, Dambacher J, Pfennig S, Brand S. rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants. PloS one 2007; 2:e819.

Type

Journal Paper/Review (English)

Journal

PloS one 2007; 2

Publication Date

Sep 5, 2007

Issn Electronic

1932-6203

Pages

e819

Brief description/objective

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 = 1.92x10(-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.

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.