Card15 and Crohn's disease: healthy homozygous carriers of the 3020insC frameshift mutation

Am J Gastroenterol. 2003 Mar;98(3):613-7. doi: 10.1111/j.1572-0241.2003.07287.x.


Objectives: Single nucleotide variations in the CARD15 gene have recently been shown to be associated with Crohn's disease (CD). Of special interest is a cytosine insertion at position 3020 of exon 11 (3020insC), which leads to a stop codon, truncation of the CARD15 protein, and an altered function of CARD15. The aim of the study was to evaluate this frameshift mutation in Dutch, multiple-affected families with inflammatory bowel disease (IBD).

Methods: Ninety-three Caucasian, multiple-affected families with IBD were recruited by interviewing patients attending our department. Sixty-one probands had CD, and 32 probands ulcerative colitis (UC). The diagnosis of probands and affected family members was verified according to standard criteria. In addition, 81 healthy, unrelated controls were included. Genomic DNA was isolated from venous blood of all participants to determine the CARD15 3020insC mutation by using an allele-specific polymerase chain reaction, followed by agarose gel electrophoresis and DNA sequencing.

Results: Association with CARD15 3020insC was statistically significant for CD, but not for UC. In one of the multiple-affected families, middle-aged and elderly homozygous carriers were identified without CD.

Conclusions: Although CARD15 3020insC appears to be etiologically important in CD, homozygous carriage does not always lead to IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Crohn Disease / genetics*
  • Cytosine / metabolism
  • Electrophoresis, Agar Gel
  • Female
  • Frameshift Mutation*
  • Genetic Predisposition to Disease
  • Homozygote
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Middle Aged
  • Nod2 Signaling Adaptor Protein
  • Pedigree
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA


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