Predisposición genética y síndrome de distrés respiratorio agudo pediátrico: nuevas herramientas de estudio genético
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2015-04
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es
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Sociedad Chilena de Pediatría
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Licencia CC
Resumen
El síndrome de distrés respiratorio agudo (SDRA) es la forma más grave de falla respiratoria. Teóricamente, cualquier noxa pulmonar aguda puede resultar en un SDRA, pero solo un pequeño porcentaje de individuos desarrolla la enfermedad. Sobre este fundamento, factores genéticos han sido implicados en el riesgo de desarrollar SDRA. Basado en la fisiopatología de esta enfermedad, múltiples genes candidatos han sido evaluados como potenciales modificadores, tanto en pacientes como en modelos animales de SDRA.
Datos experimentales y estudios clínicos recientes sugieren que variantes de genes implicados en procesos clave de daño tisular, celular y molecular pulmonar pueden influir en la predisposición y el pronóstico del SDRA. Sin embargo, la patogénesis del SDRA pediátrico es compleja y, en consecuencia, es posible anticipar que muchos genes pueden contribuir a ella. Variantes genéticas, tales como polimorfismos de nucleótido simple y variantes del número de copias, están probablemente asociadas con la predisposición al SDRA en niños con lesión pulmonar primaria. El estudio de asociación del genoma completo (GWAS, del inglés Genome-Wide Association Study) puede examinar estas variantes sin sesgos y ayudar a identificar nuevos genes fundamentales y vías patogénicas clave para futuros análisis. Esta aproximación también puede tener implicancias clínicas diagnósticas y terapéuticas, como predecir el riesgo del paciente o desarrollar un enfoque terapéutico personalizado para este grave síndrome.
Acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure. Theoretically, any acute lung condition can lead to ARDS, but only a small percentage of individuals actually develop the disease. On this basis, genetic factors have been implicated in the risk of developing ARDS. Based on the pathophysiology of this disease, many candidate genes have been evaluated as potential modifiers in patient, as well as in animal models, of ARDS. Recent experimental data and clinical studies suggest that variations of genes involved in key processes of tissue, cellular and molecular lung damage may influence susceptibility and prognosis of ARDS. However, the pathogenesis of pediatric ARDS is complex, and therefore, it can be expected that many genes might contribute. Genetic variations such as single nucleotide polymorphisms and copy-number variations are likely associated with susceptibility to ARDS in children with primary lung injury. Genome-wide association (GWA) studies can objectively examine these variations, and help identify important new genes and pathogenetic pathways for future analysis. This approach might also have diagnostic and therapeutic implications, such as predicting patient risk or developing a personalized therapeutic approach to this serious syndrome.
Acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure. Theoretically, any acute lung condition can lead to ARDS, but only a small percentage of individuals actually develop the disease. On this basis, genetic factors have been implicated in the risk of developing ARDS. Based on the pathophysiology of this disease, many candidate genes have been evaluated as potential modifiers in patient, as well as in animal models, of ARDS. Recent experimental data and clinical studies suggest that variations of genes involved in key processes of tissue, cellular and molecular lung damage may influence susceptibility and prognosis of ARDS. However, the pathogenesis of pediatric ARDS is complex, and therefore, it can be expected that many genes might contribute. Genetic variations such as single nucleotide polymorphisms and copy-number variations are likely associated with susceptibility to ARDS in children with primary lung injury. Genome-wide association (GWA) studies can objectively examine these variations, and help identify important new genes and pathogenetic pathways for future analysis. This approach might also have diagnostic and therapeutic implications, such as predicting patient risk or developing a personalized therapeutic approach to this serious syndrome.
Notas
Indexación: Web of Science; Scielo.
Palabras clave
Síndrome de distrés respiratorio agudo, Llesión pulmonar aguda, Pediatría, Genética, Polimorfismos de nucleótido simple, Estudio de asociación del genoma completo
Citación
Rev. chil. pediatr. vol.86 no.2 Santiago Apr. 2015