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Asociación de las variantes tripanolíticas de ApoL1 con enfermedad renal en afroamericanos

Giulio Genovese¹, David J Friedman, Michael D Ross

¹Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

Science (New York, N.Y.)

|July 22, 2010

Resumen

Dos variantes del gen APOL1 están vinculadas a tasas más altas de enfermedad renal en afroamericanos. Estas variantes, comunes en África, pueden ofrecer protección contra los parásitos, pero aumentan el riesgo de enfermedad renal.

Área de la Ciencia:

Genética La genética.
Nefrología Nefrología.
Biología evolutiva Biología evolutiva.

Sus antecedentes:

Los afroamericanos presentan una incidencia desproporcionadamente mayor de enfermedad renal en comparación con los estadounidenses de origen europeo.
La glomerulosclerosis segmental focal (FSGS) y la enfermedad renal en etapa terminal atribuida a la hipertensión (H-ESKD) son contribuyentes significativos a esta disparidad.

Objetivo del estudio:

Investigar la base genética para el aumento del riesgo de FSGS y H-ESKD en afroamericanos.
Para identificar variantes genéticas específicas dentro del gen APOL1 asociado con estas enfermedades renales.

Principales métodos:

Análisis de variantes de secuencia en el gen APOL1 en el cromosoma 22.
Estudios de asociación de casos y controles para determinar los coeficientes de probabilidad para FSGS y H-ESKD.
Análisis del haplotipo para evaluar la historia evolutiva y la distribución de las variantes APOL1.
Ensayos in vitro para evaluar las propiedades funcionales de las variantes de APOL1 contra el Trypanosoma brucei rhodesiense.

Principales resultados:

Dos variantes de secuencia independientes en el gen APOL1 se asociaron significativamente con un mayor riesgo de FSGS (odds ratio = 10.5) y H-ESKD (odds ratio = 7.3) en afroamericanos.
Estas variantes de APOL1 son prevalentes en las poblaciones africanas pero ausentes en las poblaciones europeas.
Las variantes APOL1 asociadas se encuentran en haplotipos que muestran señales de selección positiva.
Los estudios in vitro demostraron que solo las variantes ApoL1 asociadas a la enfermedad renal exhibieron actividad tripanolítica.

Conclusiones:

Las variantes específicas del gen APOL1 están fuertemente asociadas con la glomerulosclerosis segmental focal y la enfermedad renal en etapa terminal atribuida a la hipertensión en afroamericanos.
La selección evolutiva de las variantes APOL1, potencialmente para la protección contra la tripanosomiasis africana, puede haber llevado inadvertidamente a una mayor susceptibilidad a la enfermedad renal en poblaciones con ascendencia africana.
Estos hallazgos destacan un posible vínculo genético entre la resistencia a las enfermedades infecciosas y la prevalencia de la enfermedad renal crónica.

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