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The first gene associated with Crohn disease (CD) has been identified as CARD15 (16q12). Three variants, R702W, G908R and 1007fsinsC are strongly and independently associated with the disease. A second gene, conveying a smaller risk for inflammatory bowel disease (IBD), has been identified as DLG5 (10q23). We assess the frequency of the CARD15 SNPs and of the R30Q mutation in DLG5 and their contribution to the development of CD in a cohort of unrelated IBD patients (151 CD, 325 ulcerative colitis (UC)) and healthy controls (236) from South-east Norway (IBSEN cohort). Genotype-based tests of population differentiation using 23 SNPs across CARD15, together with estimates of F ST , indicated that the German and Norwegian background populations could be differentiated at the CARD15 locus. The Norwegian and German CD samples exhibited particularly strong differentiation at the three predisposing loci and those marking their background haplotype. There were significantly lower frequencies of the CARD15 SNPs and no significant association with CD in the Norwegian samples. Only a marginal association was observed for the subphenotypes ileitis and ileocolitis vs colitis (P ¼ 0.048). The population attributable risk percentage (PAR%) for CARD15 variants in the Norwegian cohort is the lowest reported for a European population (1.88%), except Iceland. Similarly, the DLG5 variant showed no association with CD or IBD, however, there was a negative correlation with stricture (P ¼ 0.035). The present results are consistent with an emerging pattern of a low frequency of the CARD15 variants in Northern countries where the prevalence of IBD is greatest.

Inflammatory bowel diseases (IBD) are intermittently appearing, often chronic diseases mostly affecting young people between 20-30 years of age influencing their quality of life and socioeconomic efficiency. The triggering factors for the development of IBD are not completely understood: besides environmental factors there is clear evidence for additional genetic factors influencing the risk of disease and the pattern of gut inflammation in Crohn's disease. Pathopysiological discoveries are leading to new therapeutic opportunities which are conducted in large clinical studies with main participation of the competence network IBD. The disseminated structure of the network comprising universitary and nonuniversitary hospitals and labs, the self-help-organization DCCV and its vertical cooperation with general practitioners nationwide gives opportunity to describe the diseases from the point of view of the scientist and the physician simultaneously. Therefore the competence network IBD yields the basis for the standardized integration of patient information, for the development of guidelines and the establishment of a quality management system thus leading to an improvement of scientific and clinical research.