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 23 November 2017

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News

Three NOD2 gene mutations associated with increased risk of IBD

Three NOD2 mutations have been identified that are strongly associated with Crohn's disease, claims a team from England and Germany.

News image

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The researchers analyzed a cohort of European patients with inflammatory bowel disease to determine which NOD2 gene mutations confer susceptibility to the disease.

They also looked at the degree of risk conferred by the mutations, their prevalence in familial and sporadic forms of the disease, and whether they are associated with site of disease.

The findings of the study were reported in a Rapid Communication, due to be published in the April issue of Gastroenterology.

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 IBD and 290 controls.

NOD2 mutations associated with Crohn's disease:
- R702W
- G908R
- 3020insC
Gastroenterology
Cases were stratified by disease site, and compared across NOD2 genotypes.

The team found that R702W, G908R, and 3020insC were strongly associated with Crohn's disease (CD) but not with ulcerative colitis.

Linkage disequilibrium was observed between P268S and the other mutations, forming 3 independent disease haplotypes.

Genotype relative risks were found to be 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 CD.

The frequency was also significantly increased in ileal-specific disease cases, compared with colon-specific disease (27% vs 13%).

Andrew P. Cuthbert, of Guy's, King's, and St Thomas' School of Medicine, London, England, concluded on behalf of his colleagues, "The R702W, G908R, and 3020insC mutations are strong independent risk factors for CD and are associated particularly with ileal disease."

Gastroenterology 2002; 122: 867-74
22 March 2002

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