Toll-like receptor genetic variations in bone marrow transplantation

Kaori Uchino, Shohei Mizuno, Aiko Sato-Otsubo, Yasuhito Nannya, Motonori Mizutani, Tomohiro Horio, Ichiro Hanamura, J. Luis Espinoza, Makoto Onizuka, Koichi Kashiwase, Yasuo Morishima, Takahiro Fukuda, Yoshihisa Kodera, Noriko Doki, Koichi Miyamura, Takehiko Mori, Seishi Ogawa, Akiyoshi Takami

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ > A), toll-like receptor 2 (rs7656411, 22215G > T), and toll-like receptor 4 (rs11536889, +3725G > C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor tolllike receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks.

Original languageEnglish
Pages (from-to)45670-45686
Number of pages17
JournalOncotarget
Volume8
Issue number28
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • Bone marrow transplantation
  • Single nucleotide variation
  • Toll-like receptor
  • Unrelated donor

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Uchino, K., Mizuno, S., Sato-Otsubo, A., Nannya, Y., Mizutani, M., Horio, T., Hanamura, I., Espinoza, J. L., Onizuka, M., Kashiwase, K., Morishima, Y., Fukuda, T., Kodera, Y., Doki, N., Miyamura, K., Mori, T., Ogawa, S., & Takami, A. (2017). Toll-like receptor genetic variations in bone marrow transplantation. Oncotarget, 8(28), 45670-45686. https://doi.org/10.18632/oncotarget.17315