Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients
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 <i>HO-1</i> promoter gene has one important single-nucleotide...
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MDPI AG
2020-02-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Tomohiro Horio |
| collection | DOAJ |
| description | 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 <i>HO-1</i> 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 <i>HO-1</i> expression levels than the T allele. We investigated the influence of the <i>HO-1</i> 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%; <i>p</i> = 0.03) and 5 year disease-free survival (35% vs. 22%; <i>p</i> = 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 <i>HO-1</i> rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies. |
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| language | English |
| last_indexed | 2024-03-12T06:33:44Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-13ffdda4fac64f64bbcc5fc869cb576e2023-09-03T01:27:42ZengMDPI AGCancers2072-66942020-02-0112242410.3390/cancers12020424cancers12020424Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk PatientsTomohiro Horio0Eriko Morishita1Shohei Mizuno2Kaori Uchino3Ichiro Hanamura4J. Luis Espinoza5Yasuo Morishima6Yoshihisa Kodera7Makoto Onizuka8Koichi Kashiwase9Takahiro Fukuda10Noriko Doki11Koichi Miyamura12Takehiko Mori13Shinji Nakao14Akiyoshi Takami15Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanDepartment of Clinical Laboratory Science, Kanazawa University School of Medical Sciences, Kanazawa 920-0942, JapanDivision of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanDivision of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanDivision of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanDepartment of Clinical Laboratory Science, Kanazawa University School of Medical Sciences, Kanazawa 920-0942, JapanDepartment of Promotion for Blood and Marrow Transplantation, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanHematopoietic Cell Transplantation Center, Aichi Medical University Hospital, Nagakute 480-1195, JapanDepartment of Hematology and Oncology, Tokai University School of Medicine, Isehara 259-1193, JapanJapanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo 135-8521, JapanHematopoietic Stem Cell Transplantation Unit, National Cancer Center Hospital, Tokyo 104-0045, JapanHematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo 113-8677, JapanDepartment of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya 453-8511, JapanDivision of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo 160-8582, JapanDepartment of Hematology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, JapanDivision of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, JapanHeme 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 <i>HO-1</i> 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 <i>HO-1</i> expression levels than the T allele. We investigated the influence of the <i>HO-1</i> 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%; <i>p</i> = 0.03) and 5 year disease-free survival (35% vs. 22%; <i>p</i> = 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 <i>HO-1</i> rs2071746 genotyping could be useful for selecting donors and tailoring transplant strategies for patients with high-risk hematologic malignancies.https://www.mdpi.com/2072-6694/12/2/424<i>ho-1</i>unrelated donorbone marrow transplantationsingle nucleotide polymorphism |
| spellingShingle | 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 Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients Cancers <i>ho-1</i> unrelated donor bone marrow transplantation single nucleotide polymorphism |
| title | Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients |
| title_full | Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients |
| title_fullStr | Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients |
| title_full_unstemmed | Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients |
| title_short | Donor Heme Oxygenase-1 Promoter Gene Polymorphism Predicts Survival after Unrelated Bone Marrow Transplantation for High-Risk Patients |
| title_sort | donor heme oxygenase 1 promoter gene polymorphism predicts survival after unrelated bone marrow transplantation for high risk patients |
| topic | <i>ho-1</i> unrelated donor bone marrow transplantation single nucleotide polymorphism |
| url | https://www.mdpi.com/2072-6694/12/2/424 |
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