Polimorfismo ß-2 Adrenérgico Población Mestiza Colombiana y Respuestas de la Variante Alélica Gln27Glu al Propranolol
Palabras clave:
dislipidemia, farmacogenética, polimorfismo ADRB2, propranolol, receptor ß-2 adrenérgicoResumen
XIV Premio Aventis – Área de Ciencias Básicas y Experimentales.
Los polimorfismos Arg16Gly, Gln27Glu y Thr164Ile del gen que codifica al adrenorreceptor ß-2 (ADRB2) se asocian con respuestas alteradas del sistema nervioso simpático. El propósito de este estudio fue: a) determinar las frecuencias de las tres principales variantes alélicas del gen ADRB2 en una muestra de población mestiza colombiana y compararlas con las de otros grupos étnicos; b) puesto que el receptor ADRB2 regula la movilización de lípidos, evaluar si el polimorfismo Gln27Glu constituye un riesgo para el desarrollo de dislipidemia inducida por propranolol. La genotipificación se realizó con técnicas de PCR-RFLP y se confirmó con secuenciación del DNA de muestras tomadas al azar. Para examinar la asociación entre el genotipo Gln27Glu del gen ADRB2 y dislipidemia secundaria al propranolol, se reclutaron 19 individuos sanos homocigotos para Gln27 (nativo, n=11) o para Glu27 (mutado, n=8). Las frecuencias alélicas son: Arg16 (69.7%), Gly16 (30.3%), Gln27 (68.8%), Glu27 (31.2%), Thr164 (99.3) e Ile164 (0.7%); los genotipos más frecuentes corresponden a las formas heterocigotas Gln27Glu (48.2%) y Arg16Gly (47.4%).
En la fenotipificación con propranolol encontramos que los homocigotos nativos Gln27 disminuyeron las HDL-C (p=0.005), mientras los mutados Glu27 incrementaron los niveles de triglicéridos (p=0.012), lo cual sugiere que el polimorfismo Gln27Glu, en sus formas homocigotas, representa un riesgo para dislipidemia inducida por propranolol. Estos resultados pueden contribuir a un mejor entendimiento de los mecanismos fisiopatológicos de la dislipidemia secundaria a ß-bloqueadores y a racionalizar el uso del propranolol...
Biografía del autor/a
Carlos A. Isaza Mejía, Universidad Tecnológica de Pereira
Julieta Henao, Universidad Tecnológica de Pereira
Eduardo Ramírez, Universidad Tecnológica de Pereira
Fanny Cuesta, Universidad de Antioquia
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