Toll-like receptor genetic variations in bone marrow transplantation.

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 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.

• Authors: 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
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 28 Pg. 45670-45686 (Jul 11 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28484092 (Publication Type: Journal Article)

Chemical References

• HLA Antigens
• Toll-Like Receptors

Topics

• Adolescent
• Adult
• Aged
• Alleles
• Bone Marrow Transplantation (adverse effects, methods)
• Child
• Child, Preschool
• Female
• Gene Frequency
• Genetic Variation
• Genotype
• Graft vs Host Disease (diagnosis, etiology)
• HLA Antigens (genetics, immunology)
• Hematologic Neoplasms (genetics, therapy)
• Hematopoietic Stem Cell Transplantation
• Histocompatibility Testing
• Humans
• Infant
• Infections (etiology)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Toll-Like Receptors (genetics)
• Transplantation, Homologous
• Treatment Outcome
• Unrelated Donors
• Young Adult