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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hampe
Jochen
J
Department of General Internal Medicine, Christian-Albrechts-University, Kiel, Germany.
Grebe
Jochen
J
Nikolaus
Susanna
S
Solberg
Camilla
C
Croucher
Peter J P
PJ
Mascheretti
Silvia
S
Jahnsen
Jörgen
J
Moum
Björn
B
Klump
Bodo
B
Krawczak
Michael
M
Mirza
Muddassar M
MM
Foelsch
Ulrich R
UR
Vatn
Morten
M
Schreiber
Stefan
S
D002352:Carrier Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D002885:Chromosomes, Human, Pair 16; D015331:Cohort Studies; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D053473:Nod2 Signaling Adaptor Protein; D009664:Norway; D010641:Phenotype; D012189:Retrospective Studies; D012307:Risk Factors
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein