Mutations in CARD15 and smoking confer susceptibility to Crohn's disease in the Danish population

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Mutations in CARD15 and smoking confer susceptibility to Crohn's disease in the Danish population

Authors: Anja Ernst a; Bent sen b; Mette Østergaard c; Henrik Okkels a; Vibeke Andersen c; Enrika Dagiliene b; Inge S. Pedersen a; Niels Thorsgaard d; Asbjørn M. Drewes b; Henrik B. Krarup a

Affiliations:

a Department of Clinical Biochemistry, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark

b Department of Medical Gastroenterology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark

c Department of Medicine, Viborg County Hospital, Viborg, Denmark

d Department of Medicine, Herning County Hospital, Herning, Denmark

DOI: 10.1080/00365520701427102

Publication Frequency: 12 issues per year

Published in: Scandinavian Journal of Gastroenterology, Volume 42, Issue 12 2007 , pages 1445 - 1451

Abstract

Objective. Three CAspase Recruitment Domain (CARD15) mutations have shown to predispose to Crohn's disease in Caucasian populations. The aim of this study was to investigate the mutation frequency in patients with inflammatory bowel disease and in healthy controls in Denmark.

Material and methods. Genotyping of the three common CARD15 mutations was carried out on 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls using real-time PCR. Allele and genotype frequencies in the three groups were compared. A possible additive effect of smoking on CARD15 mutations was also examined.

Results. Carrying at least one CARD15 mutation was significantly more common in patients with Crohn's disease compared with healthy controls (21% versus 10%; p <0.001). A gene-dosage effect was observed (ORadj.smoking 22.2; p<0.001 for carrying two CARD15 mutations versus ORadj.smoking 1.8; p=0.01 for carrying one CARD15 mutation). The 1007insC protein truncating mutation was the major contributing mutation. Ileal involvement was more common in Crohn's disease patients with CARD15 mutations as opposed to patients without CARD15 mutations (ORadj.smoking 3.6; p<0.001). Smoking was independently associated with Crohn's disease (OR 1.8; p<0.001), but no multiplicative effect of smoking on CARD15 genotypes was found.

Conclusions. In the Danish population, CARD15 mutations were found to be associated with Crohn's disease, hence supporting the hypothesis of a genetic component contributing to the disease. Further research for other genes possibly involved in Crohn's disease may result in the use of genetic testing for diagnosis or treatment of Crohn's disease in the future.

Keywords: CARD15; inflammatory bowel disease; phenotype; smoking