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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Epistasis between toll-like receptor-9 polymorphisms and variants in NOD2 and IL23R modulates susceptibility to crohn's disease
American Journal of Gastroenterology, Volume 104, No. 7, Year 2009
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Description
OBJECTIVES:Recent data suggest functional interactions between NOD2 and other receptors of the innate immune system modulating inflammatory responses. Here we analyzed the role of Toll-like receptor 9 (TLR-9) gene variants with respect to susceptibility to inflammatory bowel disease (IBD) and tested for genetic interactions with NOD2 and other susceptibility genes for Crohn's disease (CD).METHODS:The single-nucleotide polymorphisms (SNPs) -1237T/C (rs5743836) and 2848A/G (rs352140p.Pro545Pro) in TLR9, the main CD-associated variants within the genes for NOD2, IL23R, ATG16L1, and variants in the IBD5 locus and in the DLG5 gene were assessed in 956 patients with IBD (606 CD and 350 ulcerative colitis) and in 792 healthy controls. The associations with disease susceptibility and phenotype, and epistatic gene-gene interactions, were analyzed.RESULTS:The TLR9 1237T/C polymorphism showed significant interactions with NOD2 mutations. The frequency of 1237C was significantly higher in CD patients with at least one NOD2 mutation (P0.004 vs. controls, odds ratio (OR) 1.60, 95% confidence interval (CI) (1.15-2.21)) and further increased in CD patients with two mutated NOD2 alleles (P0.002 vs. controls, OR 2.37, 95% CI (1.35-4.15)). Significant gene-gene interactions were also observed for the TLR9 polymorphism 1237T/C with IL23R variants (most significantly with rs1004819, P0.0007), with a particular high frequency of -1237C in CD patients carrying CD-protective IL23R variants. Epistatic interactions of the TLR9 1237T/C SNP were also noted with the DLG5 113G/A variant (P0.0007).CONCLUSIONS:Our results provide evidence for genetic interactions between polymorphisms in TLR9 and CD-associated variants in NOD2, IL23R, and DLG5, differentially modulating CD susceptibility. © 2009 by the American College of Gastroenterology.
Authors & Co-Authors
Török, Helga P.
Germany, Munich
Klinikum Der Universität München
Glas, Jürgen
Germany, Munich
Klinikum Der Universität München
Germany, Munich
Ludwig-maximilians-universität München
Endres, Ilona
Germany, Munich
Ludwig-maximilians-universität München
Tonenchi, Laurian
Germany, Munich
Klinikum Der Universität München
Germany, Munich
Ludwig-maximilians-universität München
Teshome, Molla Y.
Germany, Munich
Ludwig-maximilians-universität München
Ethiopia, Jimma
Jimma University
Wetzke, Martin
Germany, Munich
Ludwig-maximilians-universität München
Klein, Wolfram
Germany, Bochum
Ruhr-universitat Bochum
Lohse, Peter
Germany, Munich
Klinikum Der Universität München
Ochsenkuḧn, Thomas
Germany, Munich
Klinikum Der Universität München
Folwaczny, Matthias
Germany, Munich
Ludwig-maximilians-universität München
Göke, Burkhard
Germany, Munich
Klinikum Der Universität München
Folwaczny, Christian
Germany, Munich
Ludwig-maximilians-universität München
Müller-Myhsok, Bertram
Germany, Munich
Max Planck Institute of Psychiatry
Brand, Stephan J.
Germany, Munich
Klinikum Der Universität München
Statistics
Citations: 78
Authors: 14
Affiliations: 5
Identifiers
Doi:
10.1038/ajg.2009.184
e-ISSN:
15720241
Research Areas
Cancer
Genetics And Genomics
Study Design
Case-Control Study