title: Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease.
abstract: OBJECTIVE
  Recent data suggest identification of causal genetic variants for inflammatory bowel disease in the DLG5 gene and in the organic cation transporter (OCTN) cluster, both situated in previously described linkage regions.
  
  
  METHODS
  The polymorphisms in DLG5 (113 G-->A, 4136 C-->A, and DLG5_e26), SLC22A4 (1672 C-->T), and SLC22A5 (-207 G-->C) were assessed in 625 patients with Crohn's disease (CD), 363 patients with ulcerative colitis (UC), and 1012 healthy controls. Association with disease susceptibility, clinical phenotypes, and possible genetic interactions of these polymorphisms with disease associated CARD15/NOD2 mutations was analysed.
  
  
  RESULTS
  No significant association of DLG5 polymorphisms with CD or UC was observed. Homozygosity for the OCTN-TC haplotype was associated with an increased CD risk (OR = 1.65), which was even greater in the presence of CARD15 mutations. Genotype-phenotype analysis revealed that this association was particularly strong in patients with colonic disease. The TC haplotype was associated with non-fistulising non-fibrostenotic disease, an earlier age of disease onset, and reduced need for surgery.
  
  
  CONCLUSIONS
  Our observations argue against a role of DLG5 polymorphisms in the susceptibility for inflammatory bowel disease, whereas the OCTN polymorphisms are associated with CD. However, due to the comparable weak association observed herein, extended linkage disequilibrium analyses of these variants with the IBD5 haplotype tagged single nucleotide polymorphims might be advisable before definitive conclusions about their causative role in CD can be drawn.
authors.affiliation: Chirurgische Klinik und Poliklinik-Standort Innenstadt, and Medizinische Poliklinik-Standort Innenstadt, Ludwig-Maximilians-Universität München, Germany.
authors.forename: H-P
authors.initials: HP
authors.lastname: Török
authors.forename: J
authors.initials: J
authors.lastname: Glas
authors.forename: L
authors.initials: L
authors.lastname: Tonenchi
authors.forename: P
authors.initials: P
authors.lastname: Lohse
authors.forename: B
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: O
authors.initials: O
authors.lastname: Limbersky
authors.forename: C
authors.initials: C
authors.lastname: Neugebauer
authors.forename: F
authors.initials: F
authors.lastname: Schnitzler
authors.forename: J
authors.initials: J
authors.lastname: Seiderer
authors.forename: C
authors.initials: C
authors.lastname: Tillack
authors.forename: S
authors.initials: S
authors.lastname: Brand
authors.forename: G
authors.initials: G
authors.lastname: Brünnler
authors.forename: P
authors.initials: P
authors.lastname: Jagiello
authors.forename: J T
authors.initials: JT
authors.lastname: Epplen
authors.forename: T
authors.initials: T
authors.lastname: Griga
authors.forename: W
authors.initials: W
authors.lastname: Klein
authors.forename: U
authors.initials: U
authors.lastname: Schiemann
authors.forename: M
authors.initials: M
authors.lastname: Folwaczny
authors.forename: T
authors.initials: T
authors.lastname: Ochsenkühn
authors.forename: C
authors.initials: C
authors.lastname: Folwaczny
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C114461:DLG5 protein, human; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D027701:Organic Cation Transport Proteins; D025521:Tumor Suppressor Proteins