title: Diverse effects of the CARD15 and IBD5 loci on clinical phenotype in 630 patients with Crohn's disease.
abstract: OBJECTIVE
  Genetic variants at the CARD15 and IBD5 loci are strongly associated with Crohn's disease (CD), but evidence of the effect of these variants on the clinical expression of CD is conflicting and has often been hampered by small sample sizes. We studied 630 well-characterized patients to clarify the genotype/phenotype relationship in CD.
  
  
  METHODS
  Patients and healthy controls were genotyped for three common mutations in CARD15 and a marker of the IBD5 risk haplotype. Allele frequencies were compared between phenotypic subgroups using chi2 or Fisher's exact tests. Genotype/phenotype analysis was carried out using multinomial logistic regression modelling allowing for adjustment for correlated or confounding factors.
  
  
  RESULTS
  The mean age at diagnosis was significantly lower in carriers of the CARD15 or IBD5 risk alleles. After correction for age and smoking, CARD15 mutations were strongly associated with both ileal disease (P=8.8 x 10(-6)) and stenotic disease (P=0.003), but the association with stenotic disease appeared to be due to a confounding effect with ileal disease. CARD15 mutations were also associated with the presence of granulomas (P=5.7 x 10(-5)), which remained significant after adjustment for age at diagnosis and disease location (P=0.0047). The IBD5 risk haplotype frequency was significantly elevated in cases with perianal disease (P=0.028) and axial spondyloarthropathy (P=0.012).
  
  
  CONCLUSIONS
  Genetic variants at the CARD15 and IBD5 loci have diverse effects on clinical expression in CD. CARD15 mutations are significantly correlated with the presence of granulomas.
authors: Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, UK.
authors: Clive M
authors: CM
authors: Onnie
authors: Sheila A
authors: SA
authors: Fisher
authors: Natalie J
authors: NJ
authors: Prescott
authors: Muddassar M
authors: MM
authors: Mirza
authors: Peter
authors: P
authors: Green
authors: Jeremy
authors: J
authors: Sanderson
authors: Alastair
authors: A
authors: Forbes
authors: Cathryn M
authors: CM
authors: Lewis
authors: Christopher G
authors: CG
authors: Mathew
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006099:Granuloma / Q000235:genetics; D006801:Humans; D007079:Ileitis / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D011183:Postoperative Complications / Q000209:etiology; D012008:Recurrence
chemical_list: D053473:Nod2 Signaling Adaptor Protein