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Pharmacogenomics. 2004 Oct;5(7):819-34.

Pharmacogenetics of methotrexate.

Author information

1
Université de Montréal, Service d'Hématologie-Oncologie, Centre de Recherche, Hôpital Sainte-Justine Département de Pédiatrie, 3175 Côte St Catherine, Montreal, Quebec, H3T 1C5, Canada. maja.krajinovic@umontreal.ca.

Abstract

Methotrexate (MTX) has proven efficient in the treatment of a number of malignancies, as well as non-malignant disorders characterized by a rapid cellular growth. Yet some patients might develop resistance, while others could have toxic side effects. MTX achieves its cytotoxicity through the inhibition of folate-dependent enzymes, suggesting that the genes controlling their activity or the levels of folate cofactors can modulate drug efficacy and, thus, the sensitivity of a patient to MTX. Indeed, several studies, conducted mostly in leukemia and rheumatoid arthritis patients, have addressed the potential for tailoring MTX therapy based on a patient's genetics. Several genetic variants have been shown to have a predictive role, among which the most frequently studied are those of methylenetetrahydrofolate reductase and thymidylate synthase genes. The other candidates, as well as gene-gene interactions, which may be even more important for the prediction of disease outcomes than the individual gene effects, are also briefly discussed.

PMID:
15469405
DOI:
10.1517/14622416.5.7.819
[Indexed for MEDLINE]

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