Predictive value of the CARD15 variant 1007fs for the diagnosis of intestinal stenoses and the need for surgery in Crohn's disease in clinical practice: results of a prospective study.
OBJECTIVE
The diagnostic and therapeutic relevance of CARD15 genotyping in Crohn's disease (CD) for daily clinical practice has not been investigated so far. We therefore analyzed whether CARD15 variants are independent predictive factors for small bowel stenosis in CD evaluated by magnetic resonance enteroclysis (MRE). On the basis of these findings, the potential implications for patient management were investigated.


METHODS
Eighty CD patients with clinical symptoms suggestive of small bowel stenosis were included. All patients were genotyped for the CARD15 variants c.2104C > T (p.R702W), c.2722G > C (p.G908R), and c.3019_3020insC (p.Leu1007fsX1008) and examined by MRE of the small bowel.


RESULTS
CARD15 variants were found in 40 (50%) patients. MRE identified 31 (38%) patients with small bowel stenoses. Twenty-five of the 40 (62%) patients with at least one CARD15 variant were diagnosed of intestinal stenosis by MRE (odds ratio [OR] = 9.44; confidence interval [CI] 3.21-27.77; P = 0.00028, Bonferroni corrected). Particularly, the presence of the 1007fs variant was associated with an increased risk of an intestinal stenosis (OR = 12.00, CI 3.47-41.54, P = 0.00042, Bonferroni corrected). Twenty-one of 31 (68%) patients with stenoses required surgical intervention, with 13 of these 21 (62%) patients carrying the 1007fs variant.


CONCLUSIONS
In the largest prospective study analyzing the diagnostic value of CARD15 variants in CD patients performed so far, we identified the 1007fs variant as strong predictor for intestinal stenoses with need for surgery in CD patients. Genotyping could therefore be an important diagnostic tool in clinical practice for identifying high-risk patients with specific diagnostic and therapeutic needs. Moreover, MRE is an excellent technique for diagnosing small bowel stenoses.
Seiderer
Julia
J
Department of Internal Medicine II-Grosshadern, University of Munich, D-81377 Munich, Germany.
Brand
Stephan
S
Herrmann
Karin A
KA
Schnitzler
Fabian
F
Hatz
Rudolf
R
Crispin
Alexander
A
Pfennig
Simone
S
Schoenberg
Stefan O
SO
Göke
Burkhard
B
Lohse
Peter
P
Ochsenkuhn
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D003424:Crohn Disease / Q000235:genetics* / Q000601:surgery*; D005260:Female; D005838:Genotype; D006801:Humans; D007415:Intestinal Obstruction / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011859:Radiography
D050505:Mutant Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein