Donor heme oxygenase-1 promoter gene polymorphism predicts survival after unrelated bone marrow transplantation for high-risk patients

Tomohiro Horio, Eriko Morishita, Shohei Mizuno, Kaori Uchino, Ichiro Hanamura, J. Luis Espinoza, Yasuo Morishima, Yoshihisa Kodera, Makoto Onizuka, Koichi Kashiwase, Takahiro Fukuda, Noriko Doki, Koichi Miyamura, Takehiko Mori, Shinji Nakao, Akiyoshi Takami

Research output: Contribution to journalArticle

Abstract

Heme oxygenase-1 (HO-1), an intracellular enzyme that catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide, exerts anti-inflammatory and cytoprotective effects against endothelial cell injury. The HO-1 promoter gene has one important single-nucleotide polymorphism (SNP) rs2071746 (-413A>T) that is functional, and the A allele has been reported to be associated with higher HO-1 expression levels than the T allele. We investigated the influence of the HO-1 rs2071746 SNP on the transplant outcomes in 593 patients with hematological malignancies undergoing unrelated, human leukocyte antigen (HLA)-matched, T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. In patients with high-risk diseases, the donor A/A or A/T genotype was associated with better 5 year overall survival (35% vs. 25%; p = 0.03) and 5 year disease-free survival (35% vs. 22%; p = 0.0072), compared to the donor T/T genotype. These effects were not observed in patients with low-risk diseases. The current findings therefore indicate that HO-1 rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.

Original languageEnglish
Article number424
JournalCancers
Volume12
Issue number2
DOIs
Publication statusPublished - 2020 Feb

Keywords

  • Bone marrow transplantation
  • HO-1
  • Single nucleotide polymorphism
  • Unrelated donor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Horio, T., Morishita, E., Mizuno, S., Uchino, K., Hanamura, I., Espinoza, J. L., Morishima, Y., Kodera, Y., Onizuka, M., Kashiwase, K., Fukuda, T., Doki, N., Miyamura, K., Mori, T., Nakao, S., & Takami, A. (2020). Donor heme oxygenase-1 promoter gene polymorphism predicts survival after unrelated bone marrow transplantation for high-risk patients. Cancers, 12(2), [424]. https://doi.org/10.3390/cancers12020424