Methylenetetrahydrofolate Reductase C677T Genotypes and Clinical Outcome Following Hematopoietic Cell Transplant

Abstract

Objective: Methotrexate may be used as a prophylactic agent against graft-versus-host disease in hematopoietic cell transplant. The drug exerts its effect on folate metabolism; 5,10-methylenetetra­hydrofolate reductase is a critical enzyme involved in this cycle and is related to the toxicity of methotrexate.

Methods: We examined the association of a single nucleotide polymorphism at position 677 in the 5,10-methylenetetrahydrofolate reductase gene and the clinical outcomes of patients treated with allogeneic hematopoietic cell transplant. Genotyping of 5,10-methylenetetrahydrofolate reductase was performed by polymerase chain reaction-restriction fragment length polymorphism on 30 patients receiving hematopoietic cell transplant and their HLA-matched related donors. Patients were given a short course of methotrexate as prophylaxis to prevent graft-versus-host disease.

Results: Donors and recipients who carried a 677T allele showed mildly higher total bilirubin, aspartic transaminase, and alanine transaminase levels, but these increases above the normal values were not statistically significant (P > .05). The platelet recovery to 20 000/µL and granulocyte recovery to 500/µL were slower for patients who carried a 677T allele, but these correlations also were not statistically significant. The 5,10-methylenetetrahy­dro­folate re­duct­ase genotypes of neither the donors nor the recipients had any effect on the incidence of acute graft-versus-host disease.

Conclusions: No association was observed between the C677T polymorphism and the outcome parameters for any of the different genotypes studied here. Additional studies with larger samples are necessary to further elucidate the influence of 5,10-methylenetetrahydrofolate reductase genotyping on clinical outcomes of patients treated with hemato­poietic cell transplant who receive methotrexate.