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

World Journal of Gastroenterology 2017年第27期23卷 4958-4967页

作者： uri netz Jane Victoria Carter Maurice Robert Eichenberger Gerald Wayne Dryden Jianmin Pan Shesh Nath Rai Susan Galandiuk Price Institute of Surgical Research the Hiram C.Polk Jr.MD Department of SurgeryUniversity of Louisville School of Medicine Department of Surgery A Soroka University Medical Center Faculty of Health Sciences Ben-Gurion University of the Negev Department of Medicine Division of GastroenterologyHepatology and Nutrition University of Louisville School of Medicine Louisville Department of Bioinformatics and Biostatistics University of Louisville School of Public Health and Information Sciences

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 wererecruited from a university digestive disease practice database. We included CD patients who received antiTNF 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). RESULTS121 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 *** The Fas-ligand SNP and TNF gene-308 SNP are associated with anti-TNF treatment response in CD and may help se

关键词：反肿瘤坏死因素船边交货 ligand 抗体反应 Crohns 疾病挑选核苷酸多型性遗传型肿瘤坏死因素基因

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