Crohn's disease: genetic susceptibility, bacteria, and innate immunity

It has long been recognised that Crohn's disease has environmental (eg, smoking) and genetic components. A sibling of a patient with Crohn's disease has a 30-fold increased risk of developing the disease compared with the general population. However, this level of risk is less than that among siblings of patients with single-gene disorders. One explanation for this difference is that many genes act to predispose to inflammatory bowel disease (IBD), and evidence supporting this hypothesis comes from genome-wide linkage studies among families with multiple affected members. The first susceptibility locus linked to Crohn's disease, IBD1 in the pericentromeric region of chromosome 16, was reported in 1996, 1 Hugot JP Laurent-Puig P Gower-Rousseau C et al. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature. 1996; 379: 821-823 Crossref PubMed Scopus (880) Google Scholar and recently confirmed in a large multicentre study. 2 Cavanaugh J The IBD International Genetics Consortium. International collaboration provides convincing linkage replication in complex disease through analysis of a large pooled data set: Crohn's disease and chromosome 16. Am J Hum Genet. 2001; 68: 1165-1171 Summary Full Text Full Text PDF PubMed Scopus (191) Google Scholar By contrast, patients with ulcerative colitis did not have evidence of linkage to IBD 1 Hugot JP Laurent-Puig P Gower-Rousseau C et al. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature. 1996; 379: 821-823 Crossref PubMed Scopus (880) Google Scholar . Three independent groups now report that mutations in a gene on chromosome 16, NOD2, are associated with Crohn's disease. 2 Cavanaugh J The IBD International Genetics Consortium. International collaboration provides convincing linkage replication in complex disease through analysis of a large pooled data set: Crohn's disease and chromosome 16. Am J Hum Genet. 2001; 68: 1165-1171 Summary Full Text Full Text PDF PubMed Scopus (191) Google Scholar , 3 Hugot JP Chamaillard M Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001; 411: 599-603 Crossref PubMed Scopus (4767) Google Scholar Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populationsThe insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis. Full-Text PDF