Ahamad, T.Armuzzi, A.Bunce, M.Mulcahy-Hawes, K.Marshall, S.E.Orchard, T.R.Crawshaw, J.Large, O.de Silva, A.Cook, J.T.Barnardo, M.Cullen, S.Welsh, K.I.Jewell, D.P.2014-10-292014-10-292002Gastroenterology. 2002; 122(4): pp.854-660016-5085 (Print)1528-0012 (Electronic)http://repository.kln.ac.lk/handle/123456789/1498Indexed in MEDLINEBACKGROUND & 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.Crohn DiseaseCrohn Disease-classificationCrohn Disease-mortalityCrohn Disease-geneticsIntracellular Signaling Peptides and ProteinsArticleMedicine