[Genotype-phenotype associations in inflammatory bowel disease]

Inflammatory bowel disease has traditionally been categorized as either ulcerative colitis or Crohn's disease on the basis of clinical, radiological and histological criteria. Emerging data suggest that inflammatory bowel disease comprises a heterogenous family of inflammatory disorders in which the specific clinical manifestations of disease are determined by the interaction of genetic and environmental factors. Interactions of susceptibility and modifying genes influence the specific features of disease phenotype, penetrance, location, behavior, and complication. CARD15/NOD2 mutations are significantly associated with ileal location, whereas certain HLA haplotypes are associated with colonic disease. The associations with CARD15/ND2 mutations and early age at onset, as well as disease behavior (stricturing, fistulizing type) are less consistent. Distinct HLA alleles contribute to the occurrence of extraintestinal manifestation. With the increasing number of genotype-phenotype relationship, it is hoped that a molecular classification can be created, in which various disease subtypes are categorized according to their specific genotypes. In the future, such sheme may permit early, accurate diagnosis, prediction of disease course, complications, prognosis, as well as treatment response.