title: Toll-like receptor 1 variation increases the risk of transplant-related mortality in hematologic malignancies.
abstract: Toll-like receptor 1 (TLR1) genetic variant (rs5743551, -7202A>G) has been reported to be associated with susceptibility to various infectious diseases. We retrospectively examined the impact of TLR1 variation on transplant outcomes in a cohort of 320 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies. A multivariate analysis showed that the G/G genotype in the recipients and the donors was associated with a significantly lower 3-year transplant-related mortality (TRM). The recipient G/G genotype also resulted in a better 3-year progression-free survival. This study suggests that the recipient and donor TLR1 G/G genotypes are comparably associated with a reduced risk of death that was not related to relapse. Thus, TLR1 genotyping may be useful for selecting the donor, managing patients in a risk-adapted manner, and creating therapeutic strategies to prevent complications after hematopoietic stem cell transplantation.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan. Electronic address: ksakai@aichi-med-u.ac.jp.
authors.forename: Kaori
authors.initials: K
authors.lastname: Uchino
authors.affiliation: Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan. Electronic address: shohei@aichi-med-u.ac.jp.
authors.forename: Shohei
authors.initials: S
authors.lastname: Mizuno
authors.affiliation: Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan. Electronic address: mtnmiz@aichi-med-u.ac.jp.
authors.forename: Motonori
authors.initials: M
authors.lastname: Mizutani
authors.affiliation: Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan. Electronic address: kuroro@aichi-med-u.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Horio
authors.affiliation: Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan. Electronic address: hanamura@aichi-med-u.ac.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hanamura
authors.affiliation: Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. Electronic address: luis@staff.kanazawa-u.ac.jp.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Espinoza
authors.affiliation: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. Electronic address: keitarom@med.kyushu-u.ac.jp.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan. Electronic address: moni5@mac.com.
authors.forename: Makoto
authors.initials: M
authors.lastname: Onizuka
authors.affiliation: Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan. Electronic address: k-kashiwase@ktks.bbc.jrc.or.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kashiwase
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. Electronic address: ymorisim@aichi-cc.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: Hematopoietic Stem Cell Transplantation Unit, National Cancer Center Hospital, Tokyo, Japan. Electronic address: tafukuda@ncc.go.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University, Nagoya, Japan. Electronic address: ykodera@river.ocn.ne.jp.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kodera
authors.affiliation: Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. Electronic address: n-doki@cick.jp.
authors.forename: Noriko
authors.initials: N
authors.lastname: Doki
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan. Electronic address: miyamu@nagoya-1st.jrc.or.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan. Electronic address: tmori@a3.keio.jp.
authors.forename: Takehiko Mori Takehiko
authors.initials: TM
authors.lastname: Mori
authors.affiliation: Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan. Electronic address: takami-knz@umin.ac.jp.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000276:immunology; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012306:Risk; D016019:Survival Analysis; D051194:Toll-Like Receptor 1 / Q000235:genetics*; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D051194:Toll-Like Receptor 1
keywords: Bone marrow transplantation; Single nucleotide variation; TLR1; Unrelated donor