The NOD2 gene and Crohn's disease: Another triumph for molecular genetics

doi:10.1016/S0016-5085(02)80138-X

Gastroenterology

Volume 122, Issue 3, March 2002, Pages 826-828

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GASTROENTEROLOGY 2002;122:826-828

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These 2 studies provide the first clear evidence for a molecular basis to a genetic association with CD. The systematic genetic search using linkage disequilibrium mapping and subsequent sequence analysis provided by Hugot et al. resulted in the identification of mutations in the NOD2 gene present only in patients with CD strongly supporting a causal relationship between mutations in NOD2 and the disease phenotype. The strength of this relationship is confirmed by the simultaneous

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Common errors in the management of the seriously ill patient with inflammatory bowel disease
2007, Gastroenterologia y Hepatologia
Reciprocal cross-talk between Nod2 and TAK1 signaling pathways
2004, Journal of Biological Chemistry
Citation Excerpt :
Crohn's disease is a chronic inflammatory bowel disease with an estimated prevalence of 1 in 1000 in Western countries (1, 2). Despite its unknown etiology, research indicates a strong association between Crohn's disease and mutation of the Nod2 (CARD15) gene (3-9). A member of the CED/APAF1 superfamily of apoptosis regulatory proteins (11), Nod2 contains two N-terminal CARD domains, a nucleotide-binding domain, and multiple C-terminal leucine-rich repeat (LRR)1 regions (10).
Mutations in the leucine-rich repeat (LRR) domain of Nod2 have been implicated in the pathogenesis of Crohn's disease, yet the function of Nod2 and regulation of the Nod2 pathway remain unclear. In this study, we determined that mitogen-activated protein kinase kinase transforming growth factor (TGF)-β-activated kinase 1 (TAK1) interacts with Nod2 and is required for Nod2-mediated NF-κB activation. The dominant negative form of TAK1 abolished muramyl dipeptide-induced NF-κB activation in Nod2-expressing cells. Nod2, acting in a reciprocal manner, inhibited TAK1-induced NF-κB activation in RICK-deficient embryonic fibroblasts. Nod2 appears to interact with TAK1 through its LRR region to exert its inhibitory effect on TAK1-induced NF-κB activation. Further, wild-type LRR more effectively suppressed NF-κB activation induced by TAK1 than LRR with a 3020insC mutation. Considered together, these findings demonstrate a critical role for TAK1 in Nod2-mediated innate immune responses and reveal a novel function for Nod2 in the regulation of the TAK1 signaling pathway.
Advances in clinical laboratory tests for inflammatory bowel disease
2003, Clinica Chimica Acta
Inflammatory bowel disease (IBD) is a generic term that refers to Crohn's disease and chronic ulcerative colitis (UC). The CD and UC are considered to be distinct forms of IBD; but there is a subgroup of CD with a UC-like presentation.
The genetic factors play a significant role in IBD. IBD is associated with a strong familial pattern. Recent studies support the hypothesis that IBD patients have a dysregulated immune response to endogenous bacteria in the gastrointestinal tract. The serologic responses seen in Crohn's disease include antibodies to Saccharomyces cerevisiae, mycobacteria, bacteroides and E. coli. The pANCA antibody seen in UC and CD has been demonstrated to react with epitopes of H1 histone, Bacteroides caccae (Ton-B linked outer membrane protein), Pseudomonas fluorescens-associated bacterial protein I-2, mycobacterial histone 1 homologue called Hup B.
In recent years, several serologic markers have been found to be useful for the diagnosis and differentiation of CD and UC. These markers include the following antibodies: (a) pANCA, (b) ASCA, (c) anti-pancreatic antibody, (d) OmpC antibody and (e) I-2 antibody and antibodies to anaerobic coccoid rods.
The application of a panel of markers with the use of an algorithm (i.e. IBD First Step) can identify specific subtypes of IBD that have different clinical courses and progression of the diseases. The serologic markers are useful for the diagnosis and management of CD and UC patients.
Dietary intake in Crohn’s disease: Results of a prospective comparative study
2014, Tunisie Medicale
Genes associated with susceptibility to ulcerative colitis
2011, World Chinese Journal of Digestology
IgA and intestinal homeostasis
2007, Mucosal Immune Defense: Immunoglobulin A

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Selected SummariesThe NOD2 gene and Crohn's disease: Another triumph for molecular genetics

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Selected Summaries
The NOD2 gene and Crohn's disease: Another triumph for molecular genetics