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Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.

Authors: Hugot, JP  Chamaillard, M  Zouali, H  Lesage, S  Cezard, JP  Belaiche, J  Almer, S  Tysk, C  O'Morain, CA  Gassull, M  Binder, V  Finkel, Y  Cortot, A  Modigliani, R  Laurent-Puig, P  Gower-Rousseau, C  Macry, J  Colombel, JF  Sahbatou, M  Thomas, G 
Citation: Hugot JP, etal., Nature. 2001 May 31;411(6837):599-603.
Pubmed: (View Article at PubMed) PMID:11385576
DOI: Full-text: DOI:10.1038/35079107

Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.

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RGD Object Information
RGD ID: 1600778
Created: 2007-03-27
Species: All species
Last Modified: 2007-03-27
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.