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Los polimorfismos genéticos de la NAD(P) H oxidasa y las proteínas de resistencia a múltiples fármacos se asocian con
Leszek Wojnowski1, Bettina Kulle, Markus Schirmer
1Department of Pharmacology, University Mainz, D-55101 Mainz, Germany. Wojnowski@uni-mainz.de
Circulation
|December 7, 2005
Resumen
Las variantes genéticas en el transporte de fármacos y el metabolismo influyen en el riesgo de cardiotoxicidad (ACT) inducida por antraciclina. La identificación de estos predictores farmacogenómicos puede ayudar a personalizar el tratamiento del cáncer y mitigar el daño cardíaco.
Área de la Ciencia:
- La farmacogenómica es la farmacogenómica.
- Cardiología Cardiología.
- Oncología Oncología.
Sus antecedentes:
- La quimioterapia con antraciclina puede causar cardiotoxicidad (ACT), lo que lleva a arritmias o insuficiencia cardíaca.
- Actualmente, no se han establecido predictores farmacogenómicos para ACT.
Objetivo del estudio:
- Investigar las variaciones genéticas como predictores de la cardiotoxicidad inducida por antraciclina (ACT).
Principales métodos:
- 1697 pacientes con linfoma no Hodgkin genotipados para polimorfismos de un solo nucleótido (SNP) en 82 genes relevantes.
- Se siguió a los pacientes durante una mediana de >3 años para registrar el desarrollo agudo y crónico de la ACT.
- Se analizaron las asociaciones entre los SNPs y la incidencia de ACT, incluidos los genes transportadores de NAD(P) H oxidasa y doxorubicina.
Principales resultados:
- Se identificaron asociaciones significativas entre la ACT y los polimorfismos en las subunidades de la NAD(P) H oxidasa (NCF4, CYBA, RAC2) y los transportadores de eflujo de doxorubicina (MRP1, MRP2).
- Las variantes específicas como NCF4 (rs1883112) y CYBA (rs4673) se relacionaron con la ACT crónica y aguda, respectivamente.
- Los ratones que carecían de actividad de la NAD(P) H oxidasa mostraron resistencia a la doxorubicina, apoyando el papel de esta vía.
Conclusiones:
- Las variantes genéticas en los genes involucrados en el transporte de doxorubicina y el metabolismo de los radicales libres se asocian con el riesgo de ACT.
- Estos hallazgos sugieren que el perfil farmacogenómico podría ayudar a predecir y administrar ACT en pacientes que reciben antraciclinas.
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