Adverse drug reaction to methotrexate: pharmacogenetic origin.
Recent advances in molecular biology have provided physicians with genetic testing strategies that can be used to predict adverse drug reactions (ADRs). Many ADRs can be linked to single-nucleotide polymorphisms in genes that control aspects of drug disposition. We report a case in which a standard dose of methotrexate resulted in life-threatening mucositis, neutropenia, and thrombocytopenia in a 61-year-old woman. The patient was found to have a genetic anomaly in an enzyme that plays a key role in folate metabolism. Methotrexate is known to deplete folate levels. As data accumulate and genetic testing strategies improve, it should be possible to predict ADRs in individual patients, thereby resulting in better patient care and a reduction in medical expenditures.
Przekop
Peter R
PR
Inland Pain Medicine, 4130 N Hallmark Parkway, San Bernardino, CA 92407-1877, USA. pprzekop@earthlink.net
Tulgan
Henry
H
Przekop
Allison A
AA
Glantz
Michael
M
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008727:Methotrexate / Q000009:adverse effects*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced / Q000473:pathology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013921:Thrombocytopenia / Q000139:chemically induced / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate