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

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.

journal_name

Scand J Gastroenterol

journal_title

Scandinavian journal of gastroenterology

authors

Ernst A,Jacobsen B,Østergaard M,Okkels H,Andersen V,Dagiliene E,Pedersen IS,Thorsgaard N,Drewes AM,Krarup HB

doi

10.1080/00365520701427102

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1445-51

issue

12

eissn

0036-5521

issn

1502-7708

pii

779331406

journal_volume

42

pub_type

杂志文章

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