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 language | English |
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Pages (from-to) | 45670-45686 |
Number of pages | 17 |
Journal | Oncotarget |
Volume | 8 |
Issue number | 28 |
DOIs | |
State | Published - 2017 |
Externally published | Yes |
Keywords
- Bone marrow transplantation
- Single nucleotide variation
- Toll-like receptor
- Unrelated donor