title: Clinical pharmacogenetics of methotrexate.
abstract: It is well known that interindividual variability can affect the response to many drugs in relation to age, gender, diet, and organ function. Pharmacogenomic studies have also documented that genetic polymorphisms can exert clinically significant effects in terms of drug resistance, efficacy and toxicity by modifying the expression of critical gene products (drug-metabolizing enzymes, transporters, and target molecules) as well as pharmacokinetic and pharmacodynamic parameters. A growing body of in vitro and clinical evidence suggests that common polymorphisms in the folate gene pathway are associated with an altered response to methotrexate (MTX) in patients with malignancy and autoimmune disease. Such polymorphisms may also induce significant MTX toxicity requiring expensive monitoring and treatment. Although the available data are not conclusive, they suggest that in the future MTX pharmacogenetics could play a key role in clinical practice by improving and tailoring treatment. This review describes the genetic polymorphisms that significantly influence MTX resistance, efficacy, and toxicity.
authors.affiliation: Department of Neuroscience, Unit of Pharmacology, School of Medicine, University Politecnica delle Marche, Ancona, Italy.
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Castaldo
authors.forename: Simona
authors.initials: S
authors.lastname: Magi
authors.forename: Annamaria Assunta
authors.initials: AA
authors.lastname: Nasti
authors.forename: Sara
authors.initials: S
authors.lastname: Arcangeli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lariccia
authors.forename: Nicola
authors.initials: N
authors.lastname: Alesi
authors.forename: Massimo
authors.initials: M
authors.lastname: Tocchini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Amoroso
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D004351:Drug Resistance; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
chemical_list: D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D008727:Methotrexate