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https://hdl.handle.net/2440/35702
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Type: | Journal article |
Title: | Donor methylenetetrahydrofolate reductase genotype is associated with graft-versus-host disease in hematopoietic stem cell transplant patients treated with methotrexate |
Author: | Murphy, N. Diviney, M. Szer, J. Bardy, P. Grigg, A. Hoyt, R. King, B. MacGregor, L. Holdsworth, R. McCluskey, J. Tait, B. |
Citation: | Bone Marrow Transplantation, 2006; 37(8):773-779 |
Publisher: | Nature Publishing Group |
Issue Date: | 2006 |
ISSN: | 0268-3369 1476-5365 |
Abstract: | Methotrexate (MTX), used as a graft-versus-host disease (GvHD) prophylactic agent in hematopoietic stem cell transplantation (HSCT), exerts its effect via folate cycle inhibition. A critical enzyme involved in folate metabolism is 5,10-methylenetetrahydrofolate reductase (MTHFR). We examined the association of a single nucleotide polymorphism (SNP) at position 677 in the MTHFR gene on GvHD outcomes in allogeneic HSCT patients administered MTX. MTHFR genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 193 HSCT patients and donors. A total of 140 patients were transplanted with an HLA-matched related donor and 53 with an unrelated donor. GvHD outcomes were compared between genotypes by univariate and multivariate analysis. The combined donor 677CT and TT genotypes were associated with a decreased incidence of GvHD (acute and chronic combined) in HSCT recipients with an HLA-matched related donor (75% at 1 year in the CT and TT group compared with 91% in the wild type CC group, P=0.01), increased time to onset of first GvHD (P=0.001) and time to first GvHD treated with systemic therapy (P=0.022). Unrelated donor MTHFR genotype was not associated with outcome parameters and no associations of recipient genotype in either related or unrelated donor cohorts were observed. |
Keywords: | Stem Cells Humans Graft vs Host Disease Methotrexate Folic Acid Methylenetetrahydrofolate Reductase (NADPH2) DNA Treatment Outcome Transplantation Conditioning Stem Cell Transplantation Hematopoietic Stem Cell Transplantation Transplantation, Homologous Multivariate Analysis Models, Statistical Proportional Hazards Models Cohort Studies Polymerase Chain Reaction Genotype Mutation Polymorphism, Restriction Fragment Length Polymorphism, Single Nucleotide Time Factors Adolescent Adult Aged Middle Aged Tissue Donors Female Male |
DOI: | 10.1038/sj.bmt.1705319 |
Published version: | http://dx.doi.org/10.1038/sj.bmt.1705319 |
Appears in Collections: | Aurora harvest 6 Medicine publications |
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