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The impact of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on transplant-related variables after allogeneic hematopoietic cell transplantation in patients receiving MTX as GVHD prophylaxis

Bone Marrow Transplantation volume 42, pages 429–430 (2008)Cite this article

Genomic screening before allogeneic hematopoietic cell transplantation has emerged as an investigational tool used to predict events that elicit subtle effects following transplantation. Single-nucleotide polymorphisms are by far the most prevalent type of variants in the human genome, with an average occurrence every several 100 bases. Most single-nucleotide polymorphisms have no known effect on gene function, but a proportion of them may alter the expression and/or biological activity of encoded proteins, contributing to variation in disease susceptibility and treatment toxicity.1

MTX is an antifolate chemotherapeutic drug used to prevent GVHD in allogeneic hematopoietic cell transplantation. MTX functions by inhibiting dihydrofolate reductase and limiting the function of other enzymes, such as methylenetetrahydrofolate reductase (MTHFR), that play roles in folate metabolism. As it has been shown that MTHFR C677T polymorphism (CT/TT) results in reduced activity of the enzyme (30% in TT and 60% in CT genotype),2, 3 use of MTX in patients with CT/TT variations may influence side effects of MTX such as mucositis and medullary toxicity acquired from low folate levels. Some studies show that the presence of the C677T (TT) genotype leads to variations in the severity of medullary and extra medullary toxicities of MTX whereas others show no effect.4, 5, 6 We assessed our data to determine if the MTHFR C677T genotype has any effect on transplant-related toxicity and engraftment kinetics in patients undergoing allogeneic hematopoietic cell transplantation who received MTX for GVHD prophylaxis.

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References

  1. Kallianpur AR . Genomic screening and complications of hematopoietic stem cell transplantation: has the time come? Bone Marrow Transplant 2005; 35: 1–16.

    Article  CAS  PubMed  Google Scholar 

  2. Ulrich CM, Yasui Y, Storb R, Schubert MM, Wagner JL, Bigler J et al. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood 2001; 98: 231–234.

    Article  CAS  PubMed  Google Scholar 

  3. Ulrich CM, Robien K, McLoad HL . Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nat Rev Cancer 2003; 3: 912–920.

    Article  CAS  PubMed  Google Scholar 

  4. Chiusolo P, Reddiconto G, Casorelli I, Laurenti L, Sora F, Mele L et al. Preponderance of methylenetetrahydrofolate reductase C677T homozygosity among leukemia patients intolerant to methotrexate. Ann Oncol 2002; 13: 1915–1918.

    Article  CAS  PubMed  Google Scholar 

  5. Robien K, Schubert MM, Bruemmer B, Lloid ME, Potter JD, Ulrich CM . Predictors of oral mucositis in patients receiving hematopoietic cell transplants for chronic myelogenous leukemia. J Clin Oncol 2004; 22: 1269–1275.

    Article  Google Scholar 

  6. Besisik-Kalayoglu S, Caliskan Y, Sargin D . Methylenetetrahydrofolate reductase C677T polymorphism and toxicity in allogeneic hematopoietic cell transplantation. Transplantation 2003; 76: 1775–1777.

    Article  Google Scholar 

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Authors and Affiliations

  1. Hematology Department, Stem Cell Transplantation Unit, Ankara University School of Medicine, Cebeci, Ankara, Turkey,

    E Soydan, P Topcuoglu, K Dalva & M Arat

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  1. E Soydan
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  2. P Topcuoglu
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  3. K Dalva
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  4. M Arat
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Correspondence to M Arat.

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Soydan, E., Topcuoglu, P., Dalva, K. et al. The impact of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism on transplant-related variables after allogeneic hematopoietic cell transplantation in patients receiving MTX as GVHD prophylaxis. Bone Marrow Transplant 42, 429–430 (2008). https://doi.org/10.1038/bmt.2008.184

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