Association of NOD2 (CARD 15) genotype with clinical course of Crohnʹs disease: a cohort study

Background Crohnʹs disease is a heterogeneous disorder for which NOD2 (CARD 15) has been identified as a susceptibility gene. We investigate the relation between NOD2 genotype and phenotypic characteristics of patients with Crohnʹs disease. Methods Hypotheses about the relation between NOD2 genotype and Crohnʹs disease phenotype were generated retrospectively from a group of 446 German patients with this disorder. Positive findings (p<0•10) were verified in prospectively established cohorts of 106 German and 55 Norwegian patients with Crohnʹs disease. All patients were genotyped for the main coding mutations in NOD2, denoted SNP8, SNP12, and SNP13, with Taqman technology. Findings In the retrospective cohort, six clinical characteristics showed noteworthy haplotype association: fistulising, ileal, left colonic and right colonic disease, stenosis, and resection. In the German prospective cohort, these haplotype associations could be replicated for ileal (p=0•006) and right colonic disease (p≤0•001). A similar trend was noted in the Norwegian patients. Interpretation We recorded a distinct relation between NOD2 genotype and phenotype of Crohnʹs disease. Test strategies with NOD2 variations to predict the clinical course of Crohnʹs disease could lead to the development of new therapeutic paradigms.