Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations

Jochen Hampe, Andrew Cuthbert, Peter J. P. Croucher, Muddassar M. Mirza, Silvia Mascheretti, Sheila Fisher, Henning Frenzel, Kathy King, Anja Hasselmeyer, Andrew J. S. MacPherson, Stephen Bridger, Sander van Deventer, Alastair Forbes, Susanna Nikolaus, John E. Lennard-Jones, Ulrich R. Foelsch, Michael Krawczak, Cathryn Lewis, Stefan Schreiber, Christopher G. Mathew

Research output: Contribution to journalArticlepeer-review

1033 Citations (Scopus)


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
Original languageEnglish
Pages (from-to)1925-1928
Number of pages4
JournalThe Lancet
Issue number9272
Publication statusPublished - 16 Jun 2001


  • Alleles
  • Carrier Proteins
  • Chromosomes, Human, Pair 16
  • Colitis, Ulcerative
  • Crohn Disease
  • England
  • Frameshift Mutation
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Germany
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mutagenesis, Insertional
  • NF-kappa B
  • Nod2 Signaling Adaptor Protein
  • Phenotype
  • Proteins

Cite this