Clinical pharmacogenomics of thiopurine S-methyltransferase

Zhou, S 2006, 'Clinical pharmacogenomics of thiopurine S-methyltransferase', Current Clinical Pharmacology, vol. 1, no. 1, pp. 119-128.


Document type: Journal Article
Collection: Journal Articles

Title Clinical pharmacogenomics of thiopurine S-methyltransferase
Author(s) Zhou, S
Year 2006
Journal name Current Clinical Pharmacology
Volume number 1
Issue number 1
Start page 119
End page 128
Total pages 10
Publisher Bentham Science Publishers Ltd.
Abstract Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP), thioguanine and azathioprine (AZA). These drugs are used to treat conditions such as acute lymphoblastic leukemia, inflammatory bowel disease, rheumatoid arthritis, and organ transplant rejection. This review highlights the polymorphisms of TPMT gene and their clinical impact on the use of thiopurine drugs. To date, there are 18 known mutational TPMT alleles. The three main TPMT alleles, namely TPMT *2, *3A and *3C, account for 80 - 95% of the intermediate and low enzyme activity. The TPMT gene exhibits significant genetic polymorphisms among all ethnic groups studied. Patients who inherited very low levels of TPMT activity are at greatly increased risk for thiopurine-induced toxicity such as myelosuppression, when treated with standard doses of these drugs, while subjects with very high activity may be undertreated. Moreover, clinical drug interactions may occur due to TMPT induction or inhibition. Identification of the TPMT mutant alleles allows physicians to tailor the dosage of the thiopurine drugs to the genotype of the patient or to use alternatives, improving therapeutic outcome.
Subject Clinical Pharmacology and Therapeutics
ISSN 1574-8847
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