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

Glas, Jürgen; Seiderer, Julia; Wetzke, Martin; Konrad, Astrid; Török, Helga-Paula; Schmechel, Silke; Tonenchi, Laurian; Grassl, Christine; Dambacher, Julia; Pfennig, Simone; Maier, Kerstin; Griga, Thomas; Klein, Wolfram; Epplen, Jörg T; Schiemann, Uwe; Folwaczny, Christian; Lohse, Peter; Göke, Burkhard; Ochsenkühn, Thomas; Müller-Myhsok, Bertram; ... (2007). 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, 2(9), e819. Lawrence, Kans.: Public Library of Science 10.1371/journal.pone.0000819

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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 = 1.92x10(-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine > Centre of Competence for General Internal Medicine

UniBE Contributor:

Schiemann, Uwe Kurt

ISSN:

1932-6203

ISBN:

17786191

Publisher:

Public Library of Science

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:01

Last Modified:

04 May 2014 23:18

Publisher DOI:

10.1371/journal.pone.0000819

PubMed ID:

17786191

Web of Science ID:

000207455500003

URI:

https://boris.unibe.ch/id/eprint/26590 (FactScience: 73615)

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