Genotype-phenotype correlations: how many disorders constitute inflammatory bowel disease?

Various chromosomal loci transfer susceptibility to the development of Crohn's disease and/or ulcerative colitis. The disease-causing gene on one of these loci (IBD1) has been identified as CARD15/NOD2 and certain loss-of-function mutations were linked to the development of Crohn's disease. The recent data from association studies of CARD15/NOD2 mutations with certain phenotypes of Crohn's disease are reviewed. These mutations link to early onset ileal and fibrostenotic disease corresponding to the A1/L1 or L3/B2 subgroup of the Vienna classification. The present data on variations in HLA or cytokine genes suggest that these genes are disease modifying rather than disease predisposing. Certainly, inflammatory bowel diseases consist of more than two genotypes and phenotypes. At this stage, predictions on the number of disease causing genes, mutations or environmental factors are impossible.