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The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease

Lookup NU author(s): Dr John Mansfield


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Background & Aims: Mutations in the NOD2 gene are strongly associated with susceptibility to Crohn's disease (CD). We analyzed a large cohort of European patients with inflammatory bowel disease to determine which mutations confer susceptibility, the degree of risk conferred, their prevalence in familial and sporadic forms of the disease, and whether they are associated with site of disease. Methods: Individuals were genotyped for 4 NOD2 mutations: P268S, R702W, G908R, and 3020insC. Allelic transmission distortion to 531 CD- and 337 ulcerative colitis-affected offspring was assessed by the transmission disequilibrium test. Association was also tested in an independent cohort of 995 patients with inflammatory bowel disease and 290 controls. Cases were stratified by disease site and compared across NOD2 genotypes. Results: R702W, G908R, and 3020insC were strongly associated with CID but not with ulcerative colitis. Linkage disequilibrium was observed between P268S and the other mutations, forming 3 independent disease haplotypes. Genotype relative risks were 3.0 for mutation heterozygotes and 23.4 for homozygotes or compound heterozygotes. The frequency of NOD2 mutations was higher in cases from families affected only with CID and was significantly increased in ileal-specific disease cases compared with colon-specific disease (26.9% vs. 12.7%, P = 0.0004). Conclusions: The R702W, G908R, and 3020insC mutations are strong independent risk factors for CD and are associated particularly with ilea[ disease.

Publication metadata

Author(s): Mansfield J; Cuthbert AP; Fisher SA; Mirza MM; King K; Hampe J; Croucher PJP; Mascheretti S; Sanderson J; Forbes A; Schreiber S; Lewis CM; Mathew CG

Publication type: Article

Publication status: Published

Journal: Gastroenterology

Year: 2002

Volume: 122

Issue: 4

Pages: 867-874

ISSN (print): 0016-5085

ISSN (electronic): 1528-0012

Publisher: W.B. Saunders Co.


DOI: 10.1053/gast.2002.32415


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Funder referenceFunder name
G9800001Medical Research Council