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Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

2013, Número 5

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Rev Invest Clin 2013; 65 (5)


Polimorfismos del gen MDR1 (ABCB1): efectos funcionales e implicaciones clínicas

Brambila-Tapia AJL

Idioma: Ingles.
Referencias bibliográficas: 55
Paginas: 445-454
Archivo PDF: 168.20 Kb.


RESUMEN

El gen MDR1 codifica para la glicoproteína P (P-gp), la cual juega un papel importante en la biodisponibilidad y limitación de la toxicidad en la célula de un amplio rango de fármacos y xenobióticos. Los tres polimorfismos de nucleótido simple (SNP) en la región codificadora (C3435T, C1236T y G2677T/ A) son los polimorfismos más ampliamente estudiados en el gen MDR1 y se han asociado con modificaciones funcionales dependientes de substrato o de inhibidor, en estudios in vitro y expresión reducida en tejidos. Los tres SNPs tienen las más altas frecuencias en asiáticos y caucásicos y las más bajas en africanos. Con respecto a las implicaciones clínicas de estos polimorfismos, se encontró en grandes meta-análisis que el polimorfismo C3435T se asoció con un leve incremento en la susceptibilidad a colitis ulcerativa y cáncer, así como con ligeras modificaciones en la farmacocinética del tacrolimus y en la respuesta a la quimioterapia basada en platino en cáncer de pulmón. Por otro lado, el polimorfismo C3435T ha mostrado resultados controversiales en la susceptibilidad a muchas otras enfermedades y la farmacocinética de drogas, donde no se han realizado meta-análisis. Existe menos información sobre los SNPs C1236T y G2677T/A, los cuales, aunque investigados en algunas enfermedades y farmacocinéticas, han sido incluidos en un número muy limitado de meta-análisis. Futuros estudios deberán incluir el análisis del haplotipo 1236T- 2677T/A-3435T, así como de otros SNPs en el gen MDR1, en otros transportadores y metabolizadores de fármacos que pudieran estar relacionados con la variable respuesta.


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