Toll-like receptor genetic variations in bone marrow transplantation

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

来源：Oncotarget, 2017, 8(28): 45670-45686.

DOI：10.18632/oncotarget.17315

• toll-like receptor
• unrelated donor
• bone marrow transplantation
• single nucleotide variation

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 toll-like 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.

• 出版日期2017-7-11