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Apolipoproteína E y la progresión de la enfermedad renal crónica
Charles C Hsu1, W H Linda Kao, Josef Coresh
1Department of Epidemiology, The Welch Center for Prevention, Epidemiology, and Clinical Research, The Johns Hopkins Medical Institutions, Baltimore, MD 21205-2223, USA.
JAMA
|June 16, 2005
Resumen
La variación genética de la apolipoproteína E (APOE) influye en la progresión de la enfermedad renal crónica (ERC). El alelo epsilon4 redujo el riesgo, mientras que el epsilon2 lo aumentó, independientemente de otros factores. Esto pone de relieve las vías no lípidas en la ERC.
Área de la Ciencia:
- Genética y Genómica.
- Nefrología Nefrología.
- Epidemiología La epidemiología.
Sus antecedentes:
- El alelo epsilon2 de la apolipoproteína E (APOE) está relacionado con un mayor riesgo de nefropatía diabética, mientras que el epsilon4 está relacionado con un menor riesgo.
- La asociación de APOE con la progresión de la enfermedad renal crónica (ERC) más allá de la nefropatía diabética sigue sin estudiarse en gran medida, especialmente en las poblaciones afroamericanas.
Objetivo del estudio:
- Para determinar el riesgo de progresión de ERC asociado con los genotipos y alelos APOE.
- Investigar estas asociaciones en una población diversa que incluye a personas blancas, afroamericanas, diabéticas y no diabéticas.
Principales métodos:
- Seguimiento prospectivo de 3859 afroamericanos y 10.661 adultos blancos (de 45 a 64 años) del estudio ARIC.
- Incidencia La progresión de la ERC definida por la hospitalización, la muerte por enfermedad renal o un aumento significativo en la creatinina sérica.
- Análisis de los genotipos y alelos de APOE en relación con la progresión de la ERC durante una mediana de 14 años.
Principales resultados:
- APOE epsilon2 aumentó moderadamente el riesgo de progresión de ERC (RR, 1.08), mientras que epsilon4 lo disminuyó (RR, 0.85), independientemente de los principales factores de riesgo y lípidos.
- APOE epsilon4 redujo significativamente el riesgo de enfermedad renal en estadio terminal (RR, 0,60).
- APOE epsilon2 se asoció con el deterioro de la función renal (RR, 1.25) pero no con eventos específicos como hospitalizaciones o ESRD.
- Las asociaciones fueron consistentes a través de la raza, el sexo, la diabetes y la hipertensión. El exceso de riesgo de ERC en los afroamericanos no se explicó por alelos APOE.
Conclusiones:
- La variación genética de APOE es un predictor significativo de la progresión de la ERC, independientemente de la diabetes, la raza y los perfiles lipídicos.
- Los hallazgos sugieren que las vías no mediadas por lípidos, que potencialmente involucran mecanismos celulares de remodelación renal, contribuyen al papel de APOE en la progresión de la ERC.
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