Evidencia de asociación entre el gen SLC6A4 y efectos epistáticos con variantes en HTR2A en la etiología del autismo en la población antioqueña

  • Ana Victoria Valencia Genética Molecular, Universidad de Antioquia, Medellín, Colombia Universidad Pontificia Bolivariana, Medellín, Colombia
  • Ana Lucía Páez Genética Molecular, Universidad de Antioquia, Medellín, Colombia
  • María Elena Sampedro Fundación Integrar, Medellín, Colombia
  • Clara Ávila Fundación Integrar, Medellín, Colombia
  • Julio Cesar Cardona Grupo Pediaciencias, Departamento de Pediatría, Escuela de Medicina, Universidad de Antioquia, Medellín, Colombia
  • Catalina Mesa Grupo Pediaciencias, Departamento de Pediatría, Escuela de Medicina, Universidad de Antioquia, Medellín, Colombia
  • Lina Galvis Grupo Pediaciencias, Departamento de Pediatría, Escuela de Medicina, Universidad de Antioquia, Medellín, Colombia
  • Jaime Carrizosa Grupo Pediaciencias, Departamento de Pediatría, Escuela de Medicina, Universidad de Antioquia, Medellín, Colombia
  • Mauricio Camargo Genética de Poblaciones, Mutacarcinogénesis y Epidemiología Genética, Universidad de Antioquia, Medellín, Colombia
  • Andrés Ruíz University College of London, Londres, Inglaterra
  • William Cornejo Universidad Pontificia Bolivariana, Medellín, Colombia Grupo Pediaciencias, Departamento de Pediatría, Escuela de Medicina, Universidad de Antioquia, Medellín, Colombia
  • Gabriel Bedoya Genética Molecular, Universidad de Antioquia, Medellín, Colombia
Palabras clave: trastorno autístico/genética, estudios de asociación genética, serotonina, polimorfismode nucleótido simple, polimorfismo genético, epístasis genética.

Resumen

Introducción. El espectro autista constituye un grupo de trastornos graves del neurodesarrollo, conun fuerte componente genético. Se ha sugerido un papel importante del sistema serotoninérgico en el desarrollo de este grupo de trastornos, con base en los estudios de respuesta a medicamentos y la hiperserotoninemia, característica común en el autismo. Se han implicado múltiples moléculas en el metabolismo y la neurotransmisión de la serotonina; sin embargo, los resultados de los estudios hantenido poca congruencia entre diferentes poblaciones.

Objetivos. Evaluar la relación entre el autismo y el polimorfismo de nucleótido simple (SingleNucleotide Polymorphism, SNP) en los genes SLC6A4, HTR2A e ITGB3, en una muestra de la población antioqueña.

Materiales y métodos. Se genotipificaron 42 núcleos familiares con autismo para 10 variantes enlos genes SLC6A4, ITGB3 y HTR2A. Se evaluó la asociación utilizando la prueba de desequilibrio enla transmisión. Se exploró el impacto de la interacción entre estos genes y el autismo, utilizando la reducción multidimensional.

Resultados. Se encontró asociación de las variantes rs4583306 (OR=2,6, p=0,004) y rs2066713(OR=2,2 p=0,03), en el gen SLC6A4, y asociación de combinaciones genotípicas entre los genes SLC6A4 y HTR2A y el riesgo de autismo (p=0,0001).

Conclusiones. Se encontró asociación significativa con variantes en el gen transportador de serotoninacon el autismo, al igual que interacción entre variantes en los genes HTR2A con SLC6A4. Estos resultados concuerdan con los de estudios previos en otras poblaciones y son pruebas a favor delpapel del sistema serotoninérgico en la etiología del espectro autista.

 

doi: http://dx.doi.org/10.7705/biomedica.v32i4.593

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Publicado
2012-12-01
Cómo citar
Valencia, A. V., Páez, A. L., Sampedro, M. E., Ávila, C., Cardona, J. C., Mesa, C., Galvis, L., Carrizosa, J., Camargo, M., Ruíz, A., Cornejo, W., & Bedoya, G. (2012). Evidencia de asociación entre el gen SLC6A4 y efectos epistáticos con variantes en HTR2A en la etiología del autismo en la población antioqueña. Biomédica, 32(4), 585-601. https://doi.org/10.7705/biomedica.v32i4.593
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