Human thiopurine S-methyltransferase pharmacogenetics: Variant allozyme misfolding and aggresome formation

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Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy.

Most medications exhibit wide interpatient variability in their efficacy and toxicity. For many medications, these interindividual differences result in part from polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and/or drug targets (eg, receptors, enzymes). Pharmacogenomics is a burgeoning field aimed at elucidating the genetic basis of differences in drug efficacy ...

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Canine red blood cell thiopurine S-methyltransferase: companion animal pharmacogenetics.

Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurine drugs. In humans, a common genetic polymorphism for TPMT is a major factor responsible for individual variation in the toxicity and therapeutic efficacy of these drugs. Dogs (Canis familiaris) are also treated with thiopurine drugs and, similar to humans, they display large individual variations in thi...

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Cat Red Blood Cell Thiopurine S-Methyltransferase: Companion Animal Pharmacogenetics

A common genetic polymorphism for thiopurine S-methyltransferase (TPMT) is a major factor responsible for individual variation in the toxicity and therapeutic efficacy of thiopurine drugs in humans. We set out to determine whether inheritance might also influence the level of TPMT activity in the domestic cat, Felis domesticus. As a first step, red blood cell (RBC) TPMT activity was measured in...

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Pharmacogenetics of thiopurine therapy: from thiopurine S-methyltransferase to S-adenosylmethionine

Background The efficiency and safety of the thiopurine therapy rely on the concentration of patient's cytotoxic thioguanine nucleotides (TGN), which in turn depend on the deactivation of thiopurine drugs by thiopurine S-methyltransferase (TPMT). The activity of TPMT largely depends on the presence of genetic polymorphisms. Determination of mutations in the TPMT gene before starting 6-mercaptopu...

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Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase.

Thiopurine drugs are used to treat patients with neoplasia and autoimmune disease as well as transplant recipients. These agents are metabolized, in part, by S-methylation catalyzed by thiopurine methyltransferase (TPMT). The discovery nearly two decades ago that levels of TPMT activity in human tissues are controlled by a common genetic polymorphism led to one of the best examples of the poten...

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ژورنال

عنوان ژورنال: Proceedings of the National Academy of Sciences

سال: 2005

ISSN: 0027-8424,1091-6490

DOI: 10.1073/pnas.0502352102