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Amanda Elizabeth Tucker1, Robert Barber1, Nicole Phillips1

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Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Las variantes genéticas en los sistemas de renina-angiotensina (RAAS) pueden influir en el riesgo de la enfermedad de Alzheimer (EA) de manera diferente entre grupos raciales. Variaciones genéticas específicas del RAAS que interactúan con APOE influyen en los resultados de la EA, lo que sugiere estrategias personalizadas de predicción de riesgos.

Palabras clave:
enfermedad de AlzheimerRAASAPOEgenéticadisparidadespoblaciones diversas

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Área de la Ciencia:

  • Genética; Neurociencia; Salud Pública

Sus antecedentes:

  • La enfermedad de Alzheimer (EA) y las demencias relacionadas (ADRD) carecen de una causa única, y los factores de riesgo como el alelo APOE ε4 y los trastornos vasculares varían en su impacto entre los grupos raciales/étnicos.; La salud vascular influye significativamente en la función cognitiva y la neurodegeneración, y las variantes genéticas en el sistema renina-angiotensina-aldosterona (RAAS) desempeñan un papel en el riesgo de enfermedad vascular.; Las interacciones potenciales entre los genes RAAS y APOE sugieren que los genes RAAS son candidatos para el estudio de interacciones gen-gen en el riesgo de EA/ADRD.

Objetivo del estudio:

  • Investigar polimorfismos de nucleótido único (SNP) específicos de la población en genes RAAS asociados con enfermedades vasculares y EA/ADRD.; Explorar posibles interacciones epistáticas entre los loci genéticos RAAS y el gen APOE en la contribución al riesgo de EA y las disparidades en la disfunción neurológica.; Identificar factores genéticos que expliquen las diferencias en el riesgo y los resultados de la EA en diversas poblaciones raciales/étnicas.

Principales métodos:

  • Se realizó un análisis de asociación genómica en el conjunto de datos del Healthy Aging Brain Study-Health Disparities (HABS-HD).; Se identificaron variantes genéticas del RAAS relacionadas con trastornos vasculares en poblaciones mexicano-americanas, negras y blancas no hispanas.; Se llevaron a cabo análisis de epistasis, frecuencia alélica y distribución de genotipos para examinar las interacciones gen-gen y su impacto en el riesgo de EA/ADRD basado en comorbilidades.

Principales resultados:

  • Se identificaron polimorfismos de nucleótido único (SNP) específicos en los loci ACE1 y AGT como candidatos para estudios translacionales y in vitro adicionales sobre epistasis.; Se encontraron SNP únicos asociados con fenotipos distintos dentro de cada cohorte racial/étnica.; Estos hallazgos sugieren que las interacciones gen-gen que involucran loci RAAS pueden contribuir a resultados diferenciales de EA.

Conclusiones:

  • Este estudio destaca la importancia de considerar la comorbilidad de enfermedades y las interacciones gen-gen, en particular la interacción entre los SNP de genes RAAS y APOE, para predecir el riesgo de EA.; Los hallazgos respaldan la necesidad de futuros estudios mecanicistas para investigar fenotipos celulares asociados con efectos epistáticos.; La comprensión de estas interacciones genéticas puede contribuir al desarrollo de estrategias más precisas para la evaluación y prevención del riesgo de EA en poblaciones diversas.