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DOCK2 está involucrado en la genética y la biología del huésped del COVID-19 grave
Ho Namkoong1, Ryuya Edahiro2,3, Tomomi Takano4
1Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.
Nature
|August 8, 2022
Resumen
Una variante genética cercana al gen DOCK2 está relacionada con el COVID-19 grave en adultos más jóvenes de Asia Oriental. Este hallazgo pone de relieve la DOCK2
Área de la Ciencia:
- Genética y genómica
- Inmunología
- Enfermedades infecciosas
Sus antecedentes:
- La identificación de los factores genéticos del huésped para el COVID-19 grave es crucial.
- Los estudios anteriores se han centrado menos en las poblaciones no europeas.
Objetivo del estudio:
- Para identificar los factores de riesgo genéticos para el COVID-19 grave en una cohorte japonesa.
- Investigar el papel del gen dedicador de la citocinesis 2 (DOCK2) en la gravedad del COVID-19.
Principales métodos:
- Estudio de asociación genómica (GWAS) de 2.393 casos de COVID-19 y 3.289 controles.
- Secuenciación de ARN (en masa y de una sola célula) y inmunohistoquímica.
- Modelo de infección de hámster sirio por SARS-CoV-2 con inhibición de DOCK2.
Principales resultados:
- Una variante de riesgo (rs60200309-A) cerca de DOCK2 se asoció con COVID-19 grave en personas menores de 65 años.
- Esta variante mostró una disminución de la expresión de DOCK2 en la sangre y los tejidos pulmonares de pacientes con COVID-19 grave.
- La inhibición de DOCK2 exacerbó la gravedad de la neumonía y la desregulación inmune en un modelo de hámster.
Conclusiones:
- DOCK2 juega un papel importante en la respuesta inmune del huésped al SARS-CoV-2.
- La variante genética identificada y la vía DOCK2 son objetivos terapéuticos potenciales para el COVID-19 grave.
- Los estudios genéticos en diversas poblaciones son vitales para comprender los mecanismos de las enfermedades.
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