Response to infliximab treatment in Crohn's disease is not associated with mutations in the CARD15 (NOD2) gene: an analysis in 534 patients from two multicenter, prospective GCP-level trials.
Infliximab induces remission in 30-40% of patients with active Crohn's disease. Treatment response is a stable trait over repeated doses yet the clinical predictors of response are still unknown. Recently, three variants in the CARD15 gene have been identified as major genetic risk factors for Crohn's disease. Single nucleotide polymorphisms (SNPs) 8, 12 and 13, have been shown to be independently associated with Crohn's disease susceptibility. The aim of the present study was to investigate these variants in relation to the therapeutic efficacy of infliximab. SNPs were genotyped (TaqMan) in two cohorts ( n= 90 and n= 444 (ACCENT I)) of active Crohn's disease patients (CDAI 220-450). The patients were recruited from independent multicenter trials conducted according to GCP. At the start of both trials, patients received a single infusion of open label infliximab (5 mg/kg bodyweight). The genotypic and allelic frequencies of each SNP were significantly associated with Crohn's disease in comparison to 370 healthy controls as reported previously. Response to infliximab (drop in CDAI 70 points or remission, respectively) was not associated with the genetic variants in the CARD15 gene in either cohort. The subsequent negative findings in a two-cohort model exclude SNPs 8, 12 and 13 of the CARD15 gene as predictors for therapeutic response to infliximab treatment.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics*; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics; D017931:DNA Primers; D005260:Female; D014644:Genetic Variation; D005858:Germany; D006801:Humans; D000069285:Infliximab; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D000069285:Infliximab