title: Contribution of the NOD1/CARD4 insertion/deletion polymorphism +32656 to inflammatory bowel disease in Northern Europe.
abstract: BACKGROUND
  NOD1/CARD4 and NOD2/CARD15 are both intracellular pattern-recognition receptors. The NOD1/CARD4 gene lies within a previously described inflammatory bowel disease (IBD) locus (7p14). An association has been suggested between the NOD1/CARD4+32656 deletion*1 variant of a complex deletion*1/insertion*2 polymorphism and IBD in 1 recent study in Europe. Our aim was to assess the influence of NOD1/CARD4+32656 on disease susceptibility and phenotype in the Scottish and Swedish IBD populations.
  
  
  METHODS
  A total of 3,962 individuals (1,791 IBD patients, 522 parents, 1,649 healthy controls) from 2 independent populations (Scotland and Sweden) were genotyped for NOD1/CARD4+32656 A/C by TaqMan and direct sequencing. Case-control, Transmission Disequilibrium Testing (TDT) and detailed genotype-phenotype (Montreal) analyses were performed. The case-control analysis had 80% power to detect an effect size of odds ratio (OR) 1.21 for IBD.
  
  
  RESULTS
  In case-control analyses in Scottish and Swedish patients, none of the genotypes studied in IBD, Crohn's disease (CD) or ulcerative colitis (UC), differed significantly from controls (deletion*1 allelic frequency 73.9%, 73.6%, 73.9%, and 73.6%, respectively: all P > 0.8). No epistatic interaction with NOD2/CARD15 was seen for CD susceptibility. TDT analysis in our Scottish early onset cohort was negative.
  
  
  CONCLUSIONS
  This variant allele of NOD1/CARD4+32656 is not associated with a strong effect on susceptibility to IBD in children and adults in Northern Europe. A gene-wide haplotype-based approach may be preferable to analysis of individual variants to assess the contribution of the NOD1/CARD4 gene to IBD.
authors.affiliation: Gastrointestinal Unit, Molecular Medicine Centre, Western General Hospital, University of Edinburgh, Edinburgh, UK.
authors.forename: J
authors.initials: J
authors.lastname: Van Limbergen
authors.forename: R K
authors.initials: RK
authors.lastname: Russell
authors.forename: E R
authors.initials: ER
authors.lastname: Nimmo
authors.forename: L
authors.initials: L
authors.lastname: Törkvist
authors.forename: C W
authors.initials: CW
authors.lastname: Lees
authors.forename: H E
authors.initials: HE
authors.lastname: Drummond
authors.forename: L
authors.initials: L
authors.lastname: Smith
authors.forename: N H
authors.initials: NH
authors.lastname: Anderson
authors.forename: P M
authors.initials: PM
authors.lastname: Gillett
authors.forename: P
authors.initials: P
authors.lastname: McGrogan
authors.forename: K
authors.initials: K
authors.lastname: Hassan
authors.forename: L T
authors.initials: LT
authors.lastname: Weaver
authors.forename: W M
authors.initials: WM
authors.lastname: Bisset
authors.forename: G
authors.initials: G
authors.lastname: Mahdi
authors.forename: I D
authors.initials: ID
authors.lastname: Arnott
authors.forename: U
authors.initials: U
authors.lastname: Sjöqvist
authors.forename: M
authors.initials: M
authors.lastname: Lördal
authors.forename: S M
authors.initials: SM
authors.lastname: Farrington
authors.forename: M G
authors.initials: MG
authors.lastname: Dunlop
authors.forename: D C
authors.initials: DC
authors.lastname: Wilson
authors.forename: J
authors.initials: J
authors.lastname: Satsangi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012606:Scotland; D013548:Sweden
chemical_list: C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein