Open AccessGenetic epistasis of IL23/IL17 pathway genes in Crohn's disease
Author(s) -
McGovern Dermot P.B.,
Rotter Jerome I.,
Mei Ling,
Haritunians Talin,
Landers Carol,
Derkowski Carrie,
Dutridge Deb,
Dubinsky Marla,
Ippoliti Andy,
Vasiliauskas Eric,
Mengesha Emebet,
King Lily,
Pressman Sheila,
Targan Stephan R.,
Taylor Kent D.
Publication year - 2009
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.20855
Subject(s) - haplotype , biology , interleukin 23 , genetics , gene , crohn's disease , disease , genetic association , genotype , interleukin 17 , single nucleotide polymorphism , medicine , cytokine
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)