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

@article{Hugot2001, abstract = {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.}, address = {Fondation Jean Dausset CEPH, 27 rue J. Dodu 75010 Paris, France.}, author = {Hugot, Jean-Pierre and Chamaillard, Mathias and Zouali, Habib and Lesage, Suzanne and Cezard, Jean-Pierre and Belaiche, Jacques and Almer, Sven and Tysk, Curt and O'Morain, Colm A. and Gassull, Miquel and Binder, Vibeke and Finkel, Yigael and Cortot, Antoine and Modigliani, Robert and Laurent-Puig, Pierre and Gower-Rousseau, Corine and Macry, Jeanne and Colombel, Jean-Frederic and Sahbatou, Mourad and Thomas, Gilles}, citeulike-article-id = {1219454}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/35079107}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/411599a0}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/11385576}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=11385576}, day = {31}, doi = {10.1038/35079107}, issn = {0028-0836}, journal = {Nature}, keywords = {association, crohn-disease, ibd}, month = {May}, number = {6837}, pages = {599--603}, posted-at = {2009-09-07 13:06:16}, priority = {4}, publisher = {Macmillian Magazines Ltd.}, title = {Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease}, url = {http://dx.doi.org/10.1038/35079107}, volume = {411}, year = {2001} }

TY - JOUR ID - Hugot2001 L3 - citeulike-article-id:1219454 N2 - 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. IS - 6837 JF - Nature SN - 0028-0836 AD - Fondation Jean Dausset CEPH, 27 rue J. Dodu 75010 Paris, France. EP - 603 TI - Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease PB - Macmillian Magazines Ltd. VL - 411 SP - 599 KW - association KW - crohn-disease KW - ibd AU - Hugot, Jean-Pierre AU - Chamaillard, Mathias AU - Zouali, Habib AU - Lesage, Suzanne AU - Cezard, Jean-Pierre AU - Belaiche, Jacques AU - Almer, Sven AU - Tysk, Curt AU - O'Morain, Colm AU - Gassull, Miquel AU - Binder, Vibeke AU - Finkel, Yigael AU - Cortot, Antoine AU - Modigliani, Robert AU - Laurent-Puig, Pierre AU - Gower-Rousseau, Corine AU - Macry, Jeanne AU - Colombel, Jean-Frederic AU - Sahbatou, Mourad AU - Thomas, Gilles PY - 2001/05/31/ UR - http://dx.doi.org/10.1038/35079107 ER -