Genetic polymorphisms predict response to anti-tumor necrosis factor treatment in Crohn's disease

Uri Netz, Jane Victoria Carter, Maurice Robert Eichenberger, Gerald Wayne Dryden, Jianmin Pan, Shesh Nath Rai, Susan Galandiuk

    Research output: Contribution to journalReview articlepeer-review

    29 Scopus citations


    Aim: To investigate genetic factors that might help define which Crohn's disease (CD) patients are likely to benefit from anti-tumor necrosis factor (TNF) therapy. Methods: This was a prospective cohort study. Patients were recruited from a university digestive disease practice database. We included CD patients who received anti-TNF therapy, had available medical records (with information on treatment duration and efficacy) and who consented to participation. Patients with allergic reactions were excluded. Patients were grouped as ever-responders or non-responders. Genomic DNA was extracted from peripheral blood, and 7 single nucleotide polymorphisms (SNPs) were assessed. The main outcome measure (following exposure to the drug) was response to therapy. The patient genotypes were assessed as the predictors of outcome. Possible confounders and effect modifiers included age, gender, race, and socioeconomic status disease, as well as disease characteristics (such as Montreal criteria). Results: 121 patients were included. Twenty-one were nonresponders, and 100 were ever-responders. Fas ligand SNP (rs763110) genotype frequencies, TNF gene -308 SNP (rs1800629) genotype frequencies, and their combination, were significantly different between groups on multivariable analysis controlling for Montreal disease behavior and perianal disease. The odds of a patient with a Fas ligand CC genotype being a non-responder were four-fold higher as compared to a TC or TT genotype (P = 0.009, OR = 4.30, 95%CI: 1.45-12.80). The presence of the A (minor) TNF gene -308 allele correlated with three-fold higher odds of being a non-responder (P = 0.049, OR = 2.88, 95%CI: 1.01-8.22). Patients with the combination of the Fas ligand CC genotype and the TNF -308 A allele had nearly five-fold higher odds of being a non-responder (P = 0.015, OR = 4.76, 95%CI: 1.35-16.77). No difference was seen for the remaining SNPs. Conclusion: The Fas-ligand SNP and TNF gene -308 SNP are associated with anti-TNF treatment response in CD and may help select patients likely to benefit from therapy.

    Original languageEnglish
    Pages (from-to)4958-4967
    Number of pages10
    JournalWorld Journal of Gastroenterology
    Issue number27
    StatePublished - 21 Jul 2017


    • Anti-tumor necrosis factor
    • Antibody
    • Crohn's disease
    • Fas ligand
    • Genotype
    • Response
    • Single nucleotide polymorphisms
    • Tumor necrosis factor gene patients likely to benefit from anti-TNF therapy

    ASJC Scopus subject areas

    • Gastroenterology


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