title: Genetic epistasis of IL23/IL17 pathway genes in Crohn's disease.
abstract: BACKGROUND
  The IL23/IL17 pathway is pivotal in the development of chronic mucosal inflammation seen in Crohn's disease (CD). Genetic variants in the IL23R and IL12B have been associated with CD susceptibility. We investigated 10 genes within the IL23/IL17 pathway in a case-control study of 763 CD cases and 254 healthy controls.
  
  
  METHODS
  We identified a novel association in haplotypes in IL17A (empirical P = 0.02), IL17RA (P = 0.001), IL17RD (P = 0.001), IL12RB1 (P = 0.003), and IL12RB2 (P = 0.001) as well as confirming the association with IL12B variants (P = 0.003).
  
  
  RESULTS
  The cumulative risk for carrying an increased number of CD risk haplotypes from genes in this pathway rises to an odds ratio of 4.3 for carrying 5 risk haplotypes. We have previously demonstrated an association between this cohort and IL23R haplotypes. Pairwise analyses suggest that there is statistical interaction between variants in IL17A and IL23R (P = 0.047) and between variants in IL17RA and IL23R (P = 0.036). Furthermore, a significant association between CD and the widely replicated IL23R variants is only seen in the presence of IL17A or IL17RA variants.
  
  
  CONCLUSIONS
  These data support the investigation of pathways implicated in CD pathogenesis in order to identify further susceptibility genes and also suggest that important gene-gene interaction is present in CD susceptibility.(Inflamm Bowel Dis 2009).
authors.affiliation: Medical Genetics Institute & Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Dermot P B
authors.initials: DP
authors.lastname: McGovern
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Ling
authors.initials: L
authors.lastname: Mei
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.forename: Carol
authors.initials: C
authors.lastname: Landers
authors.forename: Carrie
authors.initials: C
authors.lastname: Derkowski
authors.forename: Deb
authors.initials: D
authors.lastname: Dutridge
authors.forename: Marla
authors.initials: M
authors.lastname: Dubinsky
authors.forename: Andy
authors.initials: A
authors.lastname: Ippoliti
authors.forename: Eric
authors.initials: E
authors.lastname: Vasiliauskas
authors.forename: Emebet
authors.initials: E
authors.lastname: Mengesha
authors.forename: Lily
authors.initials: L
authors.lastname: King
authors.forename: Sheila
authors.initials: S
authors.lastname: Pressman
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Targan
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
mesh_terms: D016022:Case-Control Studies; D003424:Crohn Disease / Q000453:epidemiology* / Q000235:genetics*; D004843:Epistasis, Genetic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D007585:Jews / Q000235:genetics / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D053707:Receptors, Interleukin-12 / Q000235:genetics; D053722:Receptors, Interleukin-17 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C508438:IL12RB1 protein, human; C508717:IL17A protein, human; C109985:IL17RA protein, human; C515500:IL23R protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D053722:Receptors, Interleukin-17