Genetic polymorphisms of tumour necrosis factor receptor superfamily 1A and 1B affect responses to infliximab in Japanese patients with Crohn's disease

Abstract

Background: Tumour necrosis factor alpha is the key inflammatory cytokine involved in the pathogenesis of Crohn's disease. Infliximab, a chimaeric monoclonal antibody of tumour necrosis factor-α is successfully used for the treatment of Crohn's disease, although the response to infliximab therapy differs among patients. The genetic background of the individual may partially explain the differences of the responsiveness. Aim: To investigate whether the polymorphisms in these genes are associated with the response to infliximab treatment as tumour necrosis factor-α exerts its biological activity through TNF receptor superfamily 1A and 1B. Methods: Eighty Crohn's disease patients were enrolled in the study and classified into responder and nonresponder according to the efficacy of infliximab treatment. Single nucleotide polymorphisms of TNF receptor superfamily 1A (rs767455 and rs4149570) and TNF receptor superfamily 1B (rs1061622, rs1061624 and rs3397) were determined. Results: The minor allele carrier of rs767455 showed a significant association with a lack of efficacy compared to the major genotype (OR = 0.26; 95% CI: 0.08-0.91). A TNF receptor superfamily 1B haplotype inferred by rs1061624 and rs3397 also showed significant differences in the distribution between responder and nonresponder (P = 0.01). Conclusion: These results suggest that tumour necrosis factor receptor genotypes may be involved in the different responses to infliximab in Japanese patients with Crohn's disease. © 2008 The Authors.