TY - JOUR
T1 - Donor heme oxygenase-1 promoter gene polymorphism predicts survival after unrelated bone marrow transplantation for high-risk patients
AU - Horio, Tomohiro
AU - Morishita, Eriko
AU - Mizuno, Shohei
AU - Uchino, Kaori
AU - Hanamura, Ichiro
AU - Espinoza, J. Luis
AU - Morishima, Yasuo
AU - Kodera, Yoshihisa
AU - Onizuka, Makoto
AU - Kashiwase, Koichi
AU - Fukuda, Takahiro
AU - Doki, Noriko
AU - Miyamura, Koichi
AU - Mori, Takehiko
AU - Nakao, Shinji
AU - Takami, Akiyoshi
N1 - Funding Information:
Funding: This study was supported by grants from the Ministry of Education, Culture, Sports and Technology of Japan, as well as the Ministry of Health, Labor and Welfare of Japan.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2
Y1 - 2020/2
N2 - 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.
AB - 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.
KW - Bone marrow transplantation
KW - HO-1
KW - Single nucleotide polymorphism
KW - Unrelated donor
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U2 - 10.3390/cancers12020424
DO - 10.3390/cancers12020424
M3 - Article
AN - SCOPUS:85079532428
SN - 2072-6694
VL - 12
JO - Cancers
JF - Cancers
IS - 2
M1 - 424
ER -
