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Graft-Versus-Host Desease

Donor methylenetetrahydrofolate reductase genotype is associated with graft-versus-host disease in hematopoietic stem cell transplant patients treated with methotrexate

Bone Marrow Transplantation volume 37, pages 773–779 (2006)Cite this article

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.

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Acknowledgements

This study was supported by a Research Grant from the Australian Red Cross Blood Service Research Foundation.

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Authors and Affiliations

  1. Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia

    N Murphy, M Diviney, R Holdsworth & B D Tait

  2. Bone Marrow Transplant Service, Royal Melbourne Hospital, Melbourne, Australia

    J Szer, A Grigg & R Hoyt

  3. Department of Haematology, Queen Elizabeth Hospital, Woodville, South Australia, Australia

    P Bardy

  4. Clinical Epidemiology and Health Service Evaluation Unit, Melbourne Health, Melbourne, Australia

    B King & L MacGregor

  5. Department of Microbiology and Immunology, Melbourne University, Melbourne, Australia

    J McCluskey

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  1. N Murphy
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Correspondence to B D Tait.

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Murphy, N., Diviney, M., Szer, J. et al. Donor methylenetetrahydrofolate reductase genotype is associated with graft-versus-host disease in hematopoietic stem cell transplant patients treated with methotrexate. Bone Marrow Transplant 37, 773–779 (2006). https://doi.org/10.1038/sj.bmt.1705319

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