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Methylene tetrahydrofolate reductase gene polymorphisms and their association with methotrexate toxicity: a

Kalliopi P Spyridopoulou1, Niki L Dimou, Stavros J Hamodrakas

  • 1Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Greece.

Pharmacogenetics and Genomics
|December 7, 2011
PubMed
Abstract

Insights

Methylene tetrahydrofolate reductase (MTHFR) gene variations like C677T and A1298C are linked to methotrexate toxicity. These MTHFR polymorphisms show associations with adverse effects and can influence treatment outcomes in various conditions.

Area of Science:

  • Pharmacogenetics
  • Molecular Biology
  • Clinical Pharmacology

Background:

  • Methotrexate (MTX) is a widely used drug with potential adverse effects.
  • Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms may influence MTX metabolism and toxicity.
  • Understanding this association can optimize MTX therapy.

Purpose of the Study:

  • To systematically review and meta-analyze the association between MTHFR gene polymorphisms (C677T and A1298C) and MTX-related adverse effects.
  • To consolidate evidence on the role of MTHFR in MTX toxicity across different patient populations and conditions.

Main Methods:

  • Systematic literature search of PubMed for relevant studies.
  • Inclusion of 44 studies (42 unique articles) in the analysis.
  • Meta-analysis of C677T and A1298C polymorphisms using random effect models and calculation of odds ratios with 95% confidence intervals.

Main Results:

  • The C677T polymorphism was significantly associated with overall MTX toxicity, including hepatotoxicity, hematological toxicity, and neurotoxicity.
  • C677T showed an association with MTX toxicity in rheumatoid arthritis patients but a protective effect in graft-versus-host disease and hematopoietic cell transplantation.
  • The A1298C polymorphism was linked to overall MTX toxicity and demonstrated a protective role in rheumatoid arthritis patients.

Conclusions:

  • MTHFR gene polymorphisms (C677T and A1298C) are associated with MTX toxicity.
  • The specific effects can vary depending on the polymorphism and clinical context, such as rheumatoid arthritis.
  • Further research is warranted to elucidate the precise biological mechanisms underlying these associations.

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