THIOPURINE S-METHYLTRANSFERASE GENE POLYMORPHISM IS PREDICTIVE OF AZATHIOPRINE-INDUCED MYELOSUPPRESSION IN HEART TRANSPLANT RECIPIENTS
| Autor: | Philippe Boucher, Jean-Jacques Vallon, Paul Davelu, Jean Ninet, Jean-François Obadia, Pascale Boissonnat, Jacques Delaye, G. Champsaur, Georges Dureau, Laurent Sebbag |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Methyltransferase Genotype Azathioprine Pharmacology Neutropenia Thiopurine S-Methyltransferase Bone Marrow medicine Humans Genetic Predisposition to Disease Retrospective Studies Transplantation Polymorphism Genetic Leukopenia Thiopurine methyltransferase biology business.industry Methyltransferases Middle Aged medicine.disease biology.protein Heart Transplantation Female medicine.symptom business Immunosuppressive Agents Agranulocytosis Forecasting medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/00007890-200004150-00057 |
| Popis: | Azathioprine (AZA) is metabolized via the cytosolic enzyme thiopurine S-methyltransferase (TPMT). TPMT activity exhibits genetic polymorphism with four prevalent (75%) mutant alleles TPMT * 2 (G238C) and TPMT * 3 (A719G and/or G460A) and a wild-type allele TPMT * 1.To test the hypothesis that presence of these mutations is associated with greater toxicity of AZA in heart transplant recipients, 30 consecutive patients treated with AZA were followed up for the first month after heart transplant. Mutation of TPMT gene (mutation-specific polymerase chain reaction-based methods) was observed in four patients (A719G: n=2; A719G plus G460: n=2). Agranulocytosis did not occur in patients with the wild genotype. It occurred in the two patients with mutation A719G and there was a 40% drop in neutrophils in the two other patients. Discontinuation of AZA in the four mutant patients corrected for the drop. Presence of TPMT mutations is associated with a greater likelihood of agranulocytosis. Determination of these mutations could reduce the risk for hematological side-effects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|