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Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

2013, Número 2

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Rev Invest Clin 2013; 65 (2)


Análisis de los polimorfismos génicos de Tiopurina S-Metiltransferasa (TPMT) en pacientes pediátricos mexicanos con cáncer

Moreno-Guerrero SS, Ramírez-Pacheco A, Dorantes-Acosta EM, Medina-Sanson A

Idioma: Español
Referencias bibliográficas: 32
Paginas: 156-164
Archivo PDF: 208.37 Kb.


RESUMEN

Antecedentes. La Tiopurina S-Metiltransferasa (TPMT) cataliza la S-metilación de tiopurinas como la 6-mercaptopurina, 6-tioguanina y azatioprina, llevando a su inactivación. Los individuos que heredan alelos variantes del gen TPMT tienen mayor probabilidad de presentar toxicidad grave que puede poner en riesgo la vida cuando estos fármacos se administran a dosis estándar. El fenotipo silvestre TPMT*1 tiene alta actividad catalítica, mientras que todas las variantes muestran disminución de la actividad enzimática. Se han encontrado diferencias en la distribución de las variantes alélicas del gen TPMT relacionadas con el origen étnico. En México la información es limitada y hasta ahora se han publicado sólo dos estudios que muestran claras diferencias entre sí. Material y métodos. Se determinaron las variantes alélicas y genotipos del gen TPMT en 240 niños mexicanos con leucemias y tumores sólidos empleando ADN extraído de sangre periférica. Los polimorfismos G460A y A719G se identificaron por PCR-RFLP y el G238C por PCR alelo específica. Las variantes de la enzima fueron identificadas por discriminación alélica. Resultados. El genotipo homocigoto silvestre TPMT*1/ TPMT*1 se encontró en 173 pacientes (72.1%); 67 casos (27.9%) fueron heterocigotos: 18 con genotipo TPMT*1/ TPMT*3B (7.5%), 17 TPMT*1/TPMT*3C (7.1%), 16 TPMT*1/TMPT*2 (6.7%), 14 TPMT*1/TPMT*3A (5.8%) y dos (0.8%) eran homocigotos para dos variantes: TPMT*2/ TPMT*3B ambos. Las frecuencias por alelo fueron TPMT*1 en 411 (85.62%), TPMT*3B en 20 (4.1%), TPMT*2 en 18 (3.75%), TPMT*3C en 17 (3.55%) y TPMT*3A en 14 (2.9%). Conclusiones. En esta serie se encontró alta frecuencia y diversidad de genotipos variantes de TPMT, con predominio del alelo TPMT*3B.


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