title: 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.
  
  
  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.
authors.affiliation: Department of Clinical Biochemistry, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. ae@rn.dk
authors.forename: Anja
authors.initials: A
authors.lastname: Ernst
authors.forename: Bent
authors.initials: B
authors.lastname: Jacobsen
authors.forename: Mette
authors.initials: M
authors.lastname: Østergaard
authors.forename: Henrik
authors.initials: H
authors.lastname: Okkels
authors.forename: Vibeke
authors.initials: V
authors.lastname: Andersen
authors.forename: Enrika
authors.initials: E
authors.lastname: Dagiliene
authors.forename: Inge S
authors.initials: IS
authors.lastname: Pedersen
authors.forename: Niels
authors.initials: N
authors.lastname: Thorsgaard
authors.forename: Asbjørn M
authors.initials: AM
authors.lastname: Drewes
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Krarup
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology
chemical_list: D053473:Nod2 Signaling Adaptor Protein