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Densidad mineral ósea, osteoporosis y fracturas osteoporóticas: un estudio de asociación de todo el genoma
J B Richards1, F Rivadeneira, M Inouye
1Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Lancet (London, England)
|May 6, 2008
Resumen
Dos variantes genéticas cercanas a LRP5 y TNFRSF11B aumentan significativamente el riesgo de osteoporosis. Estos factores genéticos comunes contribuyen a la pérdida de densidad ósea y el riesgo de fracturas, lo que sugiere un potencial para el cribado de la población.
Área de la Ciencia:
- Genética La genética.
- Biología ósea Biología ósea Biología ósea Biología ósea
- Investigación de la osteoporosis Investigación de la osteoporosis.
Sus antecedentes:
- El diagnóstico de la osteoporosis se basa en la medición de la densidad mineral ósea (DMO).
- La DMO es un rasgo complejo influenciado por la genética y los factores ambientales.
- La identificación de los determinantes genéticos de la DMO es crucial para comprender la etiología de la osteoporosis.
Objetivo del estudio:
- Para identificar los loci genéticos asociados con la densidad mineral ósea (DMO).
- Para investigar la asociación de las variantes genéticas identificadas con las fracturas osteoporóticas.
Principales métodos:
- Estudio de asociación de todo el genoma (GWAS) de 314.075 polimorfismos de nucleótido único (SNP) en 2.094 mujeres del Reino Unido.
- Replicación de SNP prometedores en 6.463 individuos en tres cohortes europeas.
- Análisis de la expresión alélica en líneas celulares de linfoblastos.
- Pruebas de asociación con fracturas osteoporóticas utilizando datos de dos estudios independientes.
Principales resultados:
- Dos SNPs, rs4355801 (cerca de TNFRSF11B) y rs3736228 (en LRP5), mostraron una asociación significativa en todo el genoma con BMD.
- El LRP5 SNP (rs3736228) se relacionó con una disminución de la DMO y un mayor riesgo de fracturas osteoporóticas y osteoporosis.
- Los SNPs cerca de TNFRSF11B (rs4355801) se asociaron con una disminución de la DMO y un mayor riesgo de osteoporosis.
- Los alelos de riesgo eran comunes (22% de 8557 individuos), con efectos acumulados en la DMO y el riesgo de fractura.
- El análisis de la expresión alélica reveló una reducción a la mitad de la expresión de TNFRSF11B en portadores del alelo de riesgo rs4355801.
Conclusiones:
- Las variantes genéticas en LRP5 y TNFRSF11B se asocian con una disminución de la DMO y un mayor riesgo de osteoporosis y fracturas.
- El efecto combinado de estos alelos de riesgo comunes sobre el riesgo de fractura es significativo y comparable a los factores ambientales.
- La prevalencia de estos alelos de riesgo sugiere un papel potencial en las estrategias de detección de la osteoporosis.
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