期刊
BONE MARROW TRANSPLANTATION
卷 37, 期 8, 页码 773-779出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bmt.1705319
关键词
MTHFR gene; polymorphism; transplant; GvHD
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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