Clinical Pharmacogenomics of Thiopurine S-methyltransferase
Document Type
Article
Publication Date
1-2006
Keywords
genetic polymorphism, single nucleotide polymorphism (SNP), thiopurine, thiopurinemethyltransferase, toxicity
Digital Object Identifier (DOI)
https://doi.org/10.2174/157488406784111627
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 acutelymphoblastic leukemia, inflammatory bowel disease, rheumatoid arthritis, and organ transplant rejection. This reviewhighlights the polymorphisms of TPMT gene and their clinical impact on the use of thiopurine drugs. To date, there are 18known mutational TPMTalleles. The three main TPMT alleles, namely TPMT *2, *3A and *3C, account for 80 - 95% ofthe intermediate and low enzyme activity. The TPMT gene exhibits significant genetic polymorphisms among all ethnicgroups studied. Patientswho inherited very low levels of TPMT activity are at greatlyincreased risk for thiopurine-induced toxicity such as myelosuppression,when treated with standard doses of these drugs, while subjectswith very highactivity may be undertreated. Moreover, clinical drug interactions may occur due to TMPT induction or inhibition.Identification of the TPMTmutant alleles allows physicians to tailor the dosage of the thiopurine drugs to the genotype ofthe patient or to use alternatives, improving therapeutic outcome
Was this content written or created while at USF?
No
Citation / Publisher Attribution
Current Clinical Pharmacology, v. 1, issue 1, p. 119-128
Scholar Commons Citation
Zhou, Shufeng and Brink, "Clinical Pharmacogenomics of Thiopurine S-methyltransferase" (2006). Pharmacy Faculty Publications. 15.
https://digitalcommons.usf.edu/pharm_facpub/15
