Association of polymorphisms in C1orf106,IL1RN,and IL10 with post-induction infliximab trough level in Crohn’s disease patients

Background:Trough levels of the post-induction serum infliximab(IFX)are associated with short-term and long-term responses of Crohn’s disease patients to IFX,but the inter-individual differences are large.We aimed to elucidate whether single gene polymorphisms(SNPs)within FCGR3A,ATG16L1,C1orf106,OSM,OSMR,NF-jB1,IL1RN,and IL10 partially account for these differences and employed a multivariate regression model to predict patients’post-induction IFX levels.Methods:The retrospective study included 189 Crohn’s disease patients undergoing IFX therapy.Post-induction IFX levels were measured and 41 tag SNPs within eight genes were genotyped.Associations between SNPs and IFX levels were analysed.Then,a multivariate logistic-regression model was developed to predict whether the patients’IFX levels achieved the threshold of therapy(3 lg/mL).Results:Six SNPs(rs7587051,rs143063741,rs442905,rs59457695,rs3213448,and rs3021094)were significantly associated with the post-induction IFX trough level(P=0.015,P<0.001,P=0.046,P=0.022,P=0.011,P=0.013,respectively).A multivariate prediction model of the IFX level was established by baseline albumin(P=0.002),rs442905(P=0.025),rs59457695(P=0.049),rs3213448(P=0.056),and rs3021094(P=0.047).The area under the receiver operating characteristic curve(AUROC)of this prediction model in a representative training dataset was 0.758.This result was verified in a representative testing dataset,with an AUROC of 0.733.Conclusions:Polymorphisms in C1orf106,IL1RN,and IL10 play an important role in the variability of IFX post-induction levels,as indicated in this multivariate prediction model of IFX levels with fair performance.