Clinical Utility of ThiopurineS-Methyltransferase Genotyping
作者:
Hèctor Corominas,
Montserrat Baiget,
期刊:
American Journal of PharmacoGenomics
(ADIS Available online 2004)
卷期:
Volume 4,
issue 1
页码: 1-8
ISSN:1175-2203
年代: 2004
出版商: ADIS
关键词: Genetic polymorphism;Pharmacogenomics;Genotyping
数据来源: ADIS
摘要:
ThiopurineS-methyltransferase (TPMT) is a cytosolic enzyme that plays a major role in the metabolism of thiopurine drugs such as mercaptopurine and azathioprine. The interindividual differences in response to thiopurine administration is in part due to the presence of genetic polymorphisms in the gene that regulates TPMT activity.TPMTgenotype correlates well with thein vivoenzyme activity within erythrocytes. Patients with genetically determined decreased TPMT activity develop severe myelosuppression when treated with standard doses of thiopurine drugs because an excess of thioguanine nucleotides accumulates in hematopoietic tissues.TPMTgenotyping provides clinicians with a reliable method for identifying TPMT-deficient patients who can benefit from low doses of thiopurine drugs in order to reduce the risk of developing adverse effects. Moreover, the administration of higher doses of the drug could improve therapeutic response in patients in whom theTPMTgenotyping demonstrates the absence of mutated alleles.
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