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Clinical Utility of Thiopurine S-Methyltransferase Genotyping

  • Practical Pharmacogenomics
  • Published:
American Journal of Pharmacogenomics

Abstract

Thiopurine S-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. TPMT genotype correlates well with the in vivo enzyme 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.

TPMT genotyping 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 the TPMT genotyping demonstrates the absence of mutated alleles.

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Acknowledgements

The expert clinical assistance of the members of the Rheumatology Unit, Department of Internal Medicine from the Hospital de la Santa Creu i Sant Pau is gratefully acknowledged. This work was partially supported by grant SAF 2001-1055 from the Spanish Ministry of Science and Technology.

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  1. Rheumatology Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Avda. Antoni Ma Claret, 167, 08025, Barcelona, Catalonia, Spain

    Hèctor Corominas

  2. Department of Genetics, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Montserrat Baiget

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  1. Hèctor Corominas
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  2. Montserrat Baiget
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Correspondence to Hèctor Corominas.

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Corominas, H., Baiget, M. Clinical Utility of Thiopurine S-Methyltransferase Genotyping. Am J Pharmacogenomics 4, 1–8 (2004). https://doi.org/10.2165/00129785-200404010-00001

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