ESTUDIO GENÉTICO EN EL DÉFICIT DE DAO/HISTAMINOSIS

QUE SE REALIZA EN ARGENTINA

 

Es evidente que uno de los factores por los que se produce déficit de DAO es la genética. En un mismo grupo familiar, sus miembros comparten el déficit y muchas patologías crónicas tildadas hasta ahora como “hereditarias”.

La secuencia genética de la DAO se encuentra en un fragmento localizado en el cromosoma 7 (7q34-q36) del genoma humano y está compuesto por 5 exones y 4 intrones.

Se han encontrado muchas diferencias entre la secuencia de exones e intrones de este gen que son debidas a su polimorfismo genético. En total, según datos del Centro Nacional de Información Biotecnológica (NCBI), existen 85 variantes de un solo núcleotido (SNP) localizados e identificados en el gen humano de la DAO (AOC1). 17 de estos SNPs se encuentran en los exones, de los cuales 7 producen sustitución de los aminoácidos, siendo candidatos para causar alteraciones en la capacidad metabólica de la enzima.

De todos los polimorfismos encontrados en la secuencia del gen AOC1, 3 de estos polimorfismos (con referencia: rs1015611, rs1049742 y rs1049793) producen baja actividad enzimática en la metabolización de la histamina.

 

 

Personas portadoras de estos polimorfismos presentan una menor actividad de Diamino Oxidasa que individuos no portadores, siendo las diferencias en sus niveles de actividad significativas. Los estudios indican que este tipo de polimorfismos ocurren con una frecuencia global aproximada del 10-13%, afectando especialmente a mujeres de mediana edad.

Otros polimorfismos estudiados de sustitución de aminoácidos en el gen de DAO no muestran cambios en su actividad enzimática. Por otra parte, se ha asociado la variante p.T16M a un mayor riesgo de hipersensibilidad a AINES (fármacos antiinflamatorios no esteroideos), habiéndose propuesto como un biomarcador de respuesta clínica al tratamiento de patologías con estos fármacos.

 

 

Prof. Dr. Eduardo H. Raimondi

 

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