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Relación de los polimorfismos del gen paraoxonasa 1 (PON1) y la actividad funcional con el estrés oxidativo sistémico
Tamali Bhattacharyya1, Stephen J Nicholls, Eric J Topol
1Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
JAMA
|March 20, 2008
Resumen
El genotipo de la paraoxonasa 1 (PON1) influye en la actividad, lo que afecta el estrés oxidativo y el riesgo de enfermedad cardiovascular. La menor actividad de PON1 y los genotipos específicos están relacionados con un aumento de la mortalidad y los principales eventos adversos cardíacos.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Genética La genética.
- Cardiología Cardiología.
Sus antecedentes:
- La paraoxonasa 1 (PON1) exhibe propiedades antioxidantes y cardioprotectoras.
- La interacción entre los genotipos PON1, la actividad, el estrés oxidativo y el riesgo de enfermedad cardiovascular (ECV) requiere una investigación sistemática.
Objetivo del estudio:
- Explorar la asociación de factores genéticos y bioquímicos de la actividad de PON1 con marcadores sistémicos de estrés oxidativo y riesgo de ECV en humanos.
Principales métodos:
- Se evaluó a 1399 pacientes sometidos a angiografía coronaria en busca de asociaciones entre la actividad PON1, el polimorfismo Q192R, la prevalencia de ECV y futuros eventos cardíacos adversos importantes.
- Se midieron los niveles sistémicos de productos de oxidación de ácidos grasos mediante espectrometría de masas en 150 pacientes emparejados, comparándolos en función del genotipo y la actividad de PON1.
Principales resultados:
- El genotipo PON1 (QQ192 > QR192 > RR192) se correlacionó con una disminución de la actividad de PON1 y un aumento del estrés oxidativo sistémico.
- El genotipo QQ192 se asoció con mayores riesgos de mortalidad por cualquier causa (aHR, 2.05) y eventos cardíacos adversos mayores (aHR, 1.48) en comparación con RR192/QR192.
- Los cuartiles de actividad PON1 más altos mostraron una incidencia significativamente menor de eventos cardíacos adversos importantes (7.3-7.7%) frente a los cuartiles más bajos (23.5-25.1%).
Conclusiones:
- Se estableció un vínculo mecánico entre los determinantes genéticos de PON1, la actividad, el estrés oxidativo sistémico y el riesgo cardiovascular prospectivo.
- Sugiere un mecanismo potencial para la función ateroprotectora de PON1.
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