The molecular classification of the clinical manifestations of Crohn's disease

Gastroenterology. 2002 Apr;122(4):854-66. doi: 10.1053/gast.2002.32413.


Background & aims: Crohn's disease is a common inflammatory disorder of the gut characterized by variation in both location and behavior. Chromosome 16 and the HLA region on chromosome 6 have been implicated in susceptibility to disease. Mutations in the NOD2/CARD15 gene, recently identified on chromosome 16, have been associated with disease overall but are found in only 25% of patients. No data regarding their contribution to specific disease subtypes exist. Here we report a detailed genotype-phenotype analysis of 244 accurately characterized patients.

Methods: A total of 244 white patients with Crohn's disease recruited from a single center in the United Kingdom were studied. All patients were rigorously phenotyped and followed-up for a median time of 16 years. By using linkage disequilibrium mapping we studied 340 polymorphisms in 24 HLA genes and 3 NOD2/CARD15 polymorphisms.

Results: We show that NOD2/CARD15 mutations determine ileal disease only. We confirm that alleles on specific long-range HLA haplotypes determine overall susceptibility and describe novel genetic associations with susceptibility, location, and behavior of Crohn's disease.

Conclusions: The clinical pattern of Crohn's disease may be defined by specific genotypes. This study may provide the basis for a future molecular classification of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carrier Proteins / genetics
  • Child
  • Child, Preschool
  • Crohn Disease / classification*
  • Crohn Disease / genetics*
  • Crohn Disease / mortality
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-A Antigens / genetics
  • HLA-DQ Antigens / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Nod2 Signaling Adaptor Protein
  • Phenotype
  • Polymorphism, Genetic
  • Proteins / genetics
  • Survival Analysis


  • Carrier Proteins
  • HLA-A Antigens
  • HLA-DQ Antigens
  • Intracellular Signaling Peptides and Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Proteins