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Автор Weinshilboum, Richard M.
Автор Otterness, Diane M.
Автор Szumlanski, Carol L.
Дата выпуска 1999
dc.description ▪ Abstract  Methyl conjugation is an important pathway in the biotransformation of many exogenous and endogenous compounds. Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. In recent years, characterization of these genetic polymorphisms has been extended to include the cloning of cDNAs and genes, as well as a determination of the molecular basis for the effects of inheritance on these methyltransferase enzymes. The thiopurine methyltransferase genetic polymorphism is responsible for clinically significant individual variations in the toxicity and therapeutic efficacy of thiopurine drugs such as 6-mercaptopurine. Phenotyping for the thiopurine methyltransferase genetic polymorphism represents one of the first examples in which testing for a pharmacogenetic variant has entered standard clinical practice. The full functional implications of pharmacogenetic variation in the activities of catechol O-methyltransferase and histamine N-methyltransferase remain to be determined. Finally, experimental strategies used to study methylation pharmacogenetics illustrate the rapid evolution of biochemical, pharmacologic, molecular, and genomic approaches that have been used to determine the role of inheritance in variation in drug metabolism, effect, and toxicity.
Формат application.pdf
Издатель Annual Reviews
Копирайт Annual Reviews
Название METHYLATION PHARMACOGENETICS: Catechol O-Methyltransferase, Thiopurine Methyltransferase, and Histamine N-Methyltransferase
DOI 10.1146/annurev.pharmtox.39.1.19
Print ISSN 0362-1642
Журнал Annual Review of Pharmacology and Toxicology
Том 39
Первая страница 19
Последняя страница 52
Аффилиация Weinshilboum, Richard M.; Department of Pharmacology, Mayo Medical School/Mayo Clinic/Mayo Foundation, Rochester, Minnesota 55905; e-mail: weinshilboum.richard@mayo.edu

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