Genetic polymorphisms of TNF receptor superfamily 1A and 1B (TNFRSF1A and TNFRSF1B) affect responses to Infliximab in Crohn’s disease patients in Japan

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http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2036.2008.03630.x

Alimentary Pharmacology & Therapeutics

To cite this article: H. MATSUKURA, S. IKEDA, N. YOSHIMURA, M. TAKAZOE, M. MURAMATSU Genetic polymorphisms of TNF receptor superfamily 1A and 1B (TNFRSF1A and TNFRSF1B) affect responses to Infliximab in Crohn’s disease patients in Japan Alimentary Pharmacology & Therapeutics (OnlineAccepted Articles). doi:10.1111/j.1365-2036.2008.03630.x

Original Article

Genetic polymorphisms of TNF receptor superfamily 1A and 1B (TNFRSF1A and TNFRSF1B) affect responses to Infliximab in Crohn’s disease patients in Japan

H. MATSUKURA, S. IKEDA**Corresponding author: Shinobu Ikeda, Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai Chiyoda-ku, Tokyo 101-0062, Japan. Tel: +81-3-5280-8060. Fax: +81-3-5280-8061. E-mail: sikeda.epi@..., N. YOSHIMURA, M. TAKAZOE & M. MURAMATSU

H. Matsukura, S. Ikeda, M. MuramatsuDepartment of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai Chiyoda-ku, Tokyo 101-0062, JapanN. Yoshimura, M. TakazoeDivision of Gastroenterology, Social Insurance Chuo General Hospital, 3-22-1, Hyakuninn-cho, Shinjyuku-ku, Tokyo, 169-0073, Japan

*Corresponding author: Shinobu Ikeda, Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai Chiyoda-ku, Tokyo 101-0062, Japan. Tel: +81-3-5280-8060. Fax: +81-3-5280-8061. E-mail: sikeda.epi@...

Summary

Background: Tumor necrosis factor alpha (TNFα) is the key inflammatory cytokine involved in the pathogenesis of Crohn’s disease (CD). Infliximab (IFX), a chimeric monoclonal antibody of TNFα is successfully used for the treatment of CD, although the response to IFX therapy differs among patients. The genetic background of the individual may partially explain the differences of the responsiveness.

Aims: Since TNFα exerts its biological activity through TNF receptor superfamily 1A and 1B (TNFRSF1A and TNFRSF1B), we investigated whether the polymorphisms in these genes are associated with the response to IFX treatment.

Methods: Eighty CD patients were enrolled in the study and classified into responder and non-responder according to the efficacy of IFX treatment. Single nucleotide polymorphisms of TNFRSF1A (rs767455 and rs4149570) and TNFRSF1B (rs1061622, rs1061624, and rs3397) were determined.

Results: The minor allele carrier of rs767455 showed significant association with a lack of efficacy compared to the major genotype (OR = 0.26; 95%CI = 0.08-0.91). A TNFRSF1B haplotype inferred by rs1061624 and rs3397 also showed significant differences in the distribution between responder and non-responder (P = 0.01).

Conclusion: These results suggest that TNF receptor genotypes may be involved in the different responses to IFX in Japanese CD patients.