NOD2/CARD15 genotype and phenotype differences between Ashkenazi and Sephardic Jews with Crohn's disease

Am J Gastroenterol. 2004 Jun;99(6):1134-40. doi: 10.1111/j.1572-0241.2004.04156.x.


Objective: NOD2/CARD15 has been identified as a major susceptibility gene for Crohn's disease (CD). Three mutations, Arg702Trp, Gly908Arg, and Leu1007fsinsC, are associated with CD. The incidence and prevalence rate of inflammatory bowel diseases is two- to four-fold higher in Ashkenazi Jews as compared to non-Jewish Caucasians. The aim of this study was to determine the significance of the NOD2/CARD15 mutations in Jewish CD patients in Israel, and more specifically, to compare the significance of the mutations to the expression of CD in the Ashkenazi and Sephardic Jewish populations.

Methods: Allele frequencies of the mutations were determined in 180 Jewish CD patients, 73 ulcerative colitis patients, and 159 ethnically matched controls. Variants were detected using allele-specific PCR and restriction enzyme digestion assay. Demographic and phenotypic characterizations of the CD patients were determined.

Results: The carrier rate of the three mutations in the entire Jewish Israeli CD cohort is 41.1% versus 10.7% in controls (p < 0.0001). The Ashkenazi Jewish CD patients have an increased carrier rate compared to Sephardic Jews (47.4%vs 27.45%, p= 0.034). Association analyses in Ashkenazi Jews reveal odds ratios of 10.5, 9, and 4.8 for carriage of Gly908Arg, Arg702Trp, and Leu1007fsinsC mutations, respectively. Significantly higher rates of smoking, family history of inflammatory bowel diseases, and extraintestinal manifestations were found among the Sephardic CD patients.

Conclusions: NOD2/CARD15 CD-associated mutations confer increased risk mainly to the Ashkenazi Jewish CD patients in Israel. This suggests that NOD2/CARD15 mutations could contribute to the higher incidence and prevalence rates of CD among Ashkenazi Jews.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Crohn Disease / ethnology*
  • Crohn Disease / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Israel / ethnology
  • Jews / genetics*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Monte Carlo Method
  • Mutation*
  • Nod2 Signaling Adaptor Protein
  • Phenotype
  • Polymerase Chain Reaction
  • Probability
  • Sensitivity and Specificity
  • Severity of Illness Index


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein