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Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation

Genes & Immunity volume 22, pages 35–43 (2021)Cite this article

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Abstract

UNC-93 homolog B1 (UNC93B1) is a key regulator of toll-like receptors (TLRs), pattern recognition receptors that sense invading pathogens and manage the innate immune response and deliver them from the endoplasmic reticulum to their respective endosomal signaling compartments. Several types of TLRs are known to contribute to the inflammatory process after allogeneic hematopoietic stem cell transplantation (SCT), so UNC93B1 might play integral roles there. We investigated the influence of the UNC93B1 single-nucleotide polymorphism (SNP) rs308328 (T>C) on transplant outcomes in a cohort of 237 patients undergoing unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. The donor UNC93B1 C/C genotype was associated with a better 3-year overall survival than the donor UNC93B1 C/T or T/T genotype. An analysis of the UNC93B1 rs308328 genotype may therefore be useful for selecting the donor, estimating the prognosis, and creating therapeutic strategies after allogeneic SCT.

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Fig. 1: Survival outcomes after transplantation according to the donor UNC93B1 rs308328 genotype.
Fig. 2: The main causes of death were analyzed according to the UNC93B1 rs308328 genotype.

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Acknowledgements

This study was supported by grants from the Ministry of Education, Culture, Sports and Technology of Japan, a Research on Allergic Disease and Immunology (H26-106) in Health and Labor Science Grant from the Ministry of Health, Labour and Welfare of Japan, the SENSHIN Medical Research Foundation (Osaka, Japan), the Aichi Cancer Research Foundation (Nagoya, Japan), and the 24th General Assembly of the Japanese Association of Medical Sciences (Nagoya, Japan). The funders played no role in the study design, data collection, and analysis, the decision to publish, or the preparation of the manuscript. We thank all of the Japan Marrow Donor Program (JMDP) transplant teams who provided valuable assistance in caring for the patients and donors evaluated in this study. assistance in caring for the patients and donors investigated in this study.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan

    Kaori Uchino, Lam Vu Quang, Shohei Mizuno, Tomohiro Horio, Hidesuke Yamamoto, Ichiro Hanamura & Akiyoshi Takami

  2. Hematopoietic Cell Transplantation Center, Aichi Medical University Hospital, Nagakute, Japan

    Kaori Uchino, Shohei Mizuno, Tomohiro Horio, Hidesuke Yamamoto, Ichiro Hanamura, Yoshihisa Kodera & Akiyoshi Takami

  3. Division of Rehabilitation Science, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan

    J. Luis Espinoza

  4. Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan

    Makoto Onizuka

  5. Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan

    Koichi Kashiwase

  6. Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University School of Medicine, Nagakute, Japan

    Yasuo Morishima

  7. Central Japan Cord Blood Bank, Seto, Japan

    Yasuo Morishima

  8. Department of Hematology and Oncology, Nakagami Hospital, Okinawa, Japan

    Yasuo Morishima

  9. Hematopoietic Stem Cell Transplantation Unit, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

  10. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan

    Noriko Doki

  11. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Koichi Miyamura

  12. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Takehiko Mori

  13. Department of Clinical Laboratory Sciences, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan

    Eriko Morishita

  14. Department of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan

    Shinji Nakao

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  1. Kaori Uchino
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Correspondence to Akiyoshi Takami.

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Uchino, K., Vu Quang, L., Mizuno, S. et al. Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation. Genes Immun 22, 35–43 (2021). https://doi.org/10.1038/s41435-021-00122-y

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