title: CARD15 in inflammatory bowel disease and Crohn's disease phenotypes: an association study and pooled analysis.
abstract: BACKGROUND
  Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated the relation of Caspase-Activation Recruitment Domain containing protein 15 with inflammatory bowel disease and Crohn's disease phenotypic characteristics in a large Dutch cohort and performed a pooled analysis on inflammatory bowel disease patients and Crohn's disease phenotypic characteristics reported in association studies.
  
  
  METHODS
  We genotyped 781 cases and 315 controls for the R702W, G908R and 1007fsinsC variants and for six microsatellite markers in and close to Caspase-Activation Recruitment Domain containing protein 15. In the pooled analysis data of 7201 inflammatory bowel disease patients and 3720 controls from 20 studies were included.
  
  
  RESULTS
  Association was found for Crohn's disease with R702W and 1007fsinsC, including several disease characteristics, and not for ulcerative colitis. In the pooled analysis all three common Caspase-Activation Recruitment Domain containing protein 15 variants showed strong association with Crohn's disease (p<0.00001; odds ratio varying from 3.0 for single heterozygotes to 14.7 for compound heterozygotes) and not with ulcerative colitis. Phenotype analysis showed association with small bowel involvement, stricturing and penetrating disease.
  
  
  CONCLUSIONS
  Caspase-Activation Recruitment Domain containing protein 15 is associated with Crohn's disease and not with ulcerative colitis. All three common Crohn's disease-associated variants are associated with small bowel involvement, the G908R and 1007fsinsC alleles also being associated with a complicated disease course.
authors.affiliation: Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands. l.e.oostenbrug@inter.nl.net
authors.forename: L E
authors.initials: LE
authors.lastname: Oostenbrug
authors.forename: I M
authors.initials: IM
authors.lastname: Nolte
authors.forename: E
authors.initials: E
authors.lastname: Oosterom
authors.forename: G
authors.initials: G
authors.lastname: van der Steege
authors.forename: G J
authors.initials: GJ
authors.lastname: te Meerman
authors.forename: H M
authors.initials: HM
authors.lastname: van Dullemen
authors.forename: J P H
authors.initials: JP
authors.lastname: Drenth
authors.forename: D J
authors.initials: DJ
authors.lastname: de Jong
authors.forename: K
authors.initials: K
authors.lastname: van der Linde
authors.forename: P L M
authors.initials: PL
authors.lastname: Jansen
authors.forename: J H
authors.initials: JH
authors.lastname: Kleibeuker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009426:Netherlands; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein