biostudies-literatureTakahashi HYamaguchi Prefecture GovernmentJapan Society for the Promotion of Science2752https://www.ebi.ac.uk/biostudies/studies/S-EPMC8199545biostudies-literatureUnknown13(11)Unrelated bone marrow transplantation (uBMT) is performed to treat blood disorders, and it uses bone marrow from an unrelated donor as the transplant source. Although the importance of HLA matching in uBMT has been established, that of other genetic factors, such as single-nucleotide polymorphisms (SNPs), remains unclear. The application of immunoinhibitory receptors as anticancer drugs has recently been attracting attention. This prompted us to examine the importance of immunoinhibitory receptor SNPs in uBMT. We retrospectively genotyped five single-nucleotide polymorphisms (SNPs) in the immune checkpoint genes, <i>BTLA</i>, <i>PD-1</i>, <i>LAG3</i>, and <i>CTLA4</i>, and two SNPs in the methylase genes, <i>DNMT1</i> and <i>EZH2</i>, in 999 uBMT donor-recipient pairs coordinated through the Japan Marrow Donor Program matched at least at HLA-A, -B, and -DRB1. No correlations were observed between these SNPs and post-uBMT outcomes (<i>p</i> > 0.005). This result questions the usefulness of these immune checkpoint gene polymorphisms for predicting post-BMT outcomes. However, the recipient <i>EZH2</i> histone methyltransferase gene SNP, which encodes the D185H substitution, exhibited a low <i>p</i>-value in regression analysis of grade 2-4 acute graft-versus-host disease (<i>p</i> = 0.010). Due to a low minor allele frequency, this SNP warrants further investigation in a larger-scale study.CancersAnalysis of Relationships between Immune Checkpoint and Methylase Gene Polymorphisms and Outcomes after Unrelated Bone Marrow Transplantation.PMC8199545KAKENHI 26460802 and 17K09158The R & D Promotion Subsidy SystemThe R &amp; D Promotion Subsidy SystemTojo AYamasaki TMahbub MHTamada KTanabe TYamaguchi NNomura MMiyahara YOkayama NHase RTakahashi SSuehiro YMorishima YTakahashi HfalseAnalysis of Relationships between Immune Checkpoint and Methylase Gene Polymorphisms and Outcomes after Unrelated Bone Marrow Transplantation.Unrelated bone marrow transplantation (uBMT) is performed to treat blood disorders, and it uses bone marrow from an unrelated donor as the transplant source. Although the importance of HLA matching in uBMT has been established, that of other genetic factors, such as single-nucleotide polymorphisms (SNPs), remains unclear. The application of immunoinhibitory receptors as anticancer drugs has recently been attracting attention. This prompted us to examine the importance of immunoinhibitory receptor SNPs in uBMT. We retrospectively genotyped five single-nucleotide polymorphisms (SNPs) in the immune checkpoint genes, <i>BTLA</i>, <i>PD-1</i>, <i>LAG3</i>, and <i>CTLA4</i>, and two SNPs in the methylase genes, <i>DNMT1</i> and <i>EZH2</i>, in 999 uBMT donor-recipient pairs coordinated through the Japan Marrow Donor Program matched at least at HLA-A, -B, and -DRB1. No correlations were observed between these SNPs and post-uBMT outcomes (<i>p</i> > 0.005). This result questions the usefulness of these immune checkpoint gene polymorphisms for predicting post-BMT outcomes. However, the recipient <i>EZH2</i> histone methyltransferase gene SNP, which encodes the D185H substitution, exhibited a low <i>p</i>-value in regression analysis of grade 2-4 acute graft-versus-host disease (<i>p</i> = 0.010). Due to a low minor allele frequency, this SNP warrants further investigation in a larger-scale study.2021-01-01T00:00:00Z2021 Jun2026-04-08T06:54:18.468Z2022-02-10T18:05:49.682ZS-EPMC81995453420608210.3390/cancers13112752