title: rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants.
abstract: BACKGROUND
  The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants.
  
  
  METHODS
  Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T) and SLC22A5/OCTN2 (-207 G-->C).
  
  
  RESULTS
  All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5.
  
  
  CONCLUSIONS
  IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC.
authors.affiliation: Departments of Medicine II - Grosshadern, University of Munich, Munich, Germany and Clinic for Preventive Dentistry and Parodontology, University of Munich, Munich, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Glas
authors.forename: Julia
authors.initials: J
authors.lastname: Seiderer
authors.forename: Martin
authors.initials: M
authors.lastname: Wetzke
authors.forename: Astrid
authors.initials: A
authors.lastname: Konrad
authors.forename: Helga-Paula
authors.initials: HP
authors.lastname: Török
authors.forename: Silke
authors.initials: S
authors.lastname: Schmechel
authors.forename: Laurian
authors.initials: L
authors.lastname: Tonenchi
authors.forename: Christine
authors.initials: C
authors.lastname: Grassl
authors.forename: Julia
authors.initials: J
authors.lastname: Dambacher
authors.forename: Simone
authors.initials: S
authors.lastname: Pfennig
authors.forename: Kerstin
authors.initials: K
authors.lastname: Maier
authors.forename: Thomas
authors.initials: T
authors.lastname: Griga
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klein
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Epplen
authors.forename: Uwe
authors.initials: U
authors.lastname: Schiemann
authors.forename: Christian
authors.initials: C
authors.lastname: Folwaczny
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.forename: Burkhard
authors.initials: B
authors.lastname: Göke
authors.forename: Thomas
authors.initials: T
authors.lastname: Ochsenkühn
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Matthias
authors.initials: M
authors.lastname: Folwaczny
authors.forename: Thomas
authors.initials: T
authors.lastname: Mussack
authors.forename: Stephan
authors.initials: S
authors.lastname: Brand
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D003424:Crohn Disease / Q000235:genetics*; D003710:Demography; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D055815:Young Adult