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Genetic markers in methotrexate treatments
Andrea Giletti1, Patricia Esperon2
1Laboratorio de Biologia Molecular, Departamento de Bioquimica Clinica, Facultad de Quimica, Universidad de la Republica, Montevideo, Uruguay.
The Pharmacogenomics Journal
|September 22, 2018
Summary
Pharmacogenomics can help personalize methotrexate (MTX) treatment by analyzing genetic variations. Specific gene polymorphisms like MTHFR rs1801133 may guide clinical decisions for MTX therapy.
Area of Science:
- Pharmacogenomics
- Drug Metabolism
- Clinical Pharmacology
Background:
- Methotrexate (MTX) is a vital drug for cancers and autoimmune diseases.
- Interpatient variability in MTX pharmacokinetics and pharmacodynamics leads to toxicity and reduced efficacy.
- Pharmacogenomics offers a way to address MTX treatment limitations by considering genetic differences.
Purpose of the Study:
- To review the current understanding of methotrexate pharmacogenomics.
- To analyze the impact of gene polymorphisms on MTX toxicity and efficacy across various diseases.
- To identify specific genetic markers that may influence clinical decision-making for MTX therapy.
Main Methods:
- Literature review of studies on MTX pharmacogenomics.
- Analysis of gene polymorphisms involved in MTX influx, efflux, cellular effects, and elimination.
- Evaluation of the association between genetic variations and MTX clinical outcomes.
Main Results:
- Several gene polymorphisms influence MTX pharmacokinetics and pharmacodynamics.
- Polymorphisms in genes related to MTX transport and metabolism affect treatment outcomes.
- The review highlights the complex interplay between genetics and MTX response.
Conclusions:
- Only MTHFR rs1801133, SLC19A1 rs1051266, and TYMS rs34743033 gene polymorphisms show potential for influencing clinical decisions in MTX therapy.
- Personalized medicine approaches using pharmacogenomics can optimize MTX treatment.
- Further research is needed to fully elucidate the clinical utility of these genetic markers.
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