Association of NOD2 (CARD 15) genotype with clinical course of Crohn's disease: a cohort study.

Authors:
Jochen Hampe, Jochen Grebe, Susanna Nikolaus, Camilla Solberg, Peter J P Croucher, Silvia Mascheretti, Jörgen Jahnsen, Björn Moum, Bodo Klump, Michael Krawczak, Muddassar M Mirza, Ulrich R Foelsch, Morten Vatn, Stefan Schreiber
Year of publication:
2002
Volume:
359
Issue:
9318
Issn:
0140-6736
Journal title abbreviated:
LANCET
Journal title long:
Lancet : a journal of British and foreign medicine, surgery ... <et al.> : in two volumes annually
Impact factor:
44.002
Abstract:
Crohn''s 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 Crohn''s disease.Hypotheses about the relation between NOD2 genotype and Crohn''s 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 Crohn''s disease. All patients were genotyped for the main coding mutations in NOD2, denoted SNP8, SNP12, and SNP13, with Taqman technology.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 < or =0.001). A similar trend was noted in the Norwegian patients.We recorded a distinct relation between NOD2 genotype and phenotype of Crohn''s disease. Test strategies with NOD2 variations to predict the clinical course of Crohn''s disease could lead to the development of new therapeutic paradigms.