Document Detail


Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations.
MedLine Citation:
PMID:  11425413     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Background Genetic predisposition to inflammatory bowel disease (IBD) has been shown by epidemiological and linkage studies. Genetic linkage of IBD to chromosome 16 has been previously observed and replicated in independent populations. The recently identified NOD2 gene is a good positional and functional candidate gene since it is located in the region of linkage on chromosome 16q12, and activates nuclear factor (NF) kappaB in response to bacterial lipopolysaccharides. Methods We sequenced the coding region of the NOD2 gene and genotyped an insertion polymorphism affecting the leucine-rich region of the protein product in 512 individuals with IBD from 309 German or British families, 369 German trios (ie, German patients with sporadic IBD and their unaffected parents), and 272 normal controls. We then tested for association with Crohn's disease and ulcerative colitis. Findings Family-based association analyses were consistently positive in 95 British and 99 German affected sibling pairs with Crohn's disease (combined p<0.0001); the association was confirmed in the 304 German trios with Crohn's disease. No association was seen in the 115 sibling pairs and 65 trios with ulcerative colitis. The genotype-specific disease risks conferred by heterozygous and homozygous mutant genotypes were 2.6 (95% CI 1.5-4.5) and 42.1 (4.3-infinity), respectively. Interpretation The insertion mutation in the NOD2 gene confers a substantially increased susceptibility to Crohn's disease but not to ulcerative colitis.
Authors:
J Hampe; A Cuthbert; P J Croucher; M M Mirza; S Mascheretti; S Fisher; H Frenzel; K King; A Hasselmeyer; A J MacPherson; S Bridger; S van Deventer; A Forbes; S Nikolaus; J E Lennard-Jones; U R Foelsch; M Krawczak; C Lewis; S Schreiber; C G Mathew
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Lancet     Volume:  357     ISSN:  0140-6736     ISO Abbreviation:  Lancet     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-06-26     Completed Date:  2001-07-12     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  1925-8     Citation Subset:  AIM; IM    
Affiliation:
Department of General Internal Medicine, Christian-Albrechts-University, Kiel, Germany.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Carrier Proteins*
Chromosomes, Human, Pair 16*
Colitis, Ulcerative / genetics
Crohn Disease / genetics*
England
Frameshift Mutation / genetics
Gene Frequency / genetics
Genetic Predisposition to Disease / genetics
Genotype
Germany
Humans
Intracellular Signaling Peptides and Proteins*
Mutagenesis, Insertional / genetics*
NF-kappa B / genetics
Nod2 Signaling Adaptor Protein
Phenotype
Proteins / genetics*
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/NF-kappa B; 0/NOD2 protein, human; 0/Nod2 Signaling Adaptor Protein; 0/Proteins
Comments/Corrections
Comment In:
Lancet. 2001 Jun 16;357(9272):1902-4   [PMID:  11425408 ]
Erratum In:
Lancet 2002 Sep 7;360(9335):806

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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