title: Association of organic cation transporter risk haplotype with perianal penetrating Crohn's disease but not with susceptibility to IBD.
abstract: OBJECTIVE
  Three years after the identification of NOD2/CARD15, 2 more genes for inflammatory bowel diseases (IBDs) were reported. The carnitine/organic cation transporter (OCTN) on 5q31 (IBD5) is associated with Crohn's disease (CD) and DLG5 (10q23), a member of membrane-associated guanylate kinase (MAGUK) family, with IBD. We studied mutation prevalence, assessed phenotypic expression, and performed conditional analysis to examine evidence for gene-gene interactions.
  
  
  METHODS
  A cohort of 2032 individuals was genotyped for disease-associated OCTN and DLG5 variants, including 981 patients with IBD (CD, n = 769; ulcerative colitis, n = 186; indeterminate colitis, n = 26) followed up at a tertiary IBD center. For 373 patients, DNA from both parents was available (cohort 1) for transmission disequilibrium testing analysis; case-control analysis was performed in 608 patients and 305 controls (cohort 2).
  
  
  RESULTS
  There was no distortion of transmission toward affected offspring for any of the variant alleles. Case-control analysis also failed to shown an association. A higher frequency of DLG5 113A was observed in CARD15-positive patients (12.2%) compared with CARD15-negative patients (8.7%; P = .033). The OCTN-TC risk haplotype was associated with penetrating disease (odds ratio, 1.474; 95% confidence interval, 1.028-2.114; P = .035). For DLG5, there were no associations with a particular phenotype.
  
  
  CONCLUSIONS
  DLG5 and OCTN do not play a role in the susceptibility to IBD, CD, or ulcerative colitis in the Flemish population but play a role in the phenotypic expression of the disease. OCTN variants were associated with perianal and penetrating CD. More studies in independent populations are urgently needed to assess the validity of DLG5 and OCTN in the pathogenesis of IBD.
authors.affiliation: Department of Gastroenterology, UZ Gasthuisberg, Leuven, Belgium. severine.vermeire@uz.kuleuven.ac.be
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Marie
authors.initials: M
authors.lastname: Pierik
authors.forename: Tibor
authors.initials: T
authors.lastname: Hlavaty
authors.forename: Greet
authors.initials: G
authors.lastname: Claessens
authors.forename: Nele
authors.initials: N
authors.lastname: van Schuerbeeck
authors.forename: Sofie
authors.initials: S
authors.lastname: Joossens
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
authors.forename: Liesbet
authors.initials: L
authors.lastname: Henckaerts
authors.forename: Mirjam
authors.initials: M
authors.lastname: Bueno de Mesquita
authors.forename: Robert
authors.initials: R
authors.lastname: Vlietinck
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D002877:Chromosomes, Human; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D003424:Crohn Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype
chemical_list: D027701:Organic Cation Transport Proteins