Medical College of Wisconsin
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Genetic epistasis of IL23/IL17 pathway genes in Crohn's disease. Inflamm Bowel Dis 2009 Jun;15(6):883-9

Date

02/25/2009

Pubmed ID

19235914

Pubmed Central ID

PMC2916929

DOI

10.1002/ibd.20855

Scopus ID

2-s2.0-67650255063 (requires institutional sign-in at Scopus site)   66 Citations

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).

Author List

McGovern DP, Rotter JI, Mei L, Haritunians T, Landers C, Derkowski C, Dutridge D, Dubinsky M, Ippoliti A, Vasiliauskas E, Mengesha E, King L, Pressman S, Targan SR, Taylor KD

Author

Ling Mei MD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Case-Control Studies
Crohn Disease
Epistasis, Genetic
Genetic Predisposition to Disease
Haplotypes
Humans
Interleukin-17
Jews
Polymorphism, Single Nucleotide
Receptors, Interleukin
Receptors, Interleukin-12
Receptors, Interleukin-17
Risk Factors