Next-Generation Sequencing of PTGS Genes Reveals an Increased Frequency of Non-synonymous Variants Among Patients With NSAID-Induced Liver Injury.

Purpose: The etiopathogenesis of drug-induced liver injury (DILI) is still far from being elucidated. This study aims to the study of genetic variations in DILI, related to the drug target, and specifically in the genes coding for the cyclooxygenase enzymes. Methods: By using Next-generation Sequenc...

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Detalles Bibliográficos
Autores: Lucena, María Isabel, García-Martín, Elena, Daly, Ann K, Blanca, Miguel, Andrade, Raúl J, Agúndez, José A G
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17822
Acceso en línea:http://hdl.handle.net/20.500.12105/17822
Access Level:acceso abierto
Palabra clave:COX1
COX2
PTGS1
PTGS2
Drug-induced liver injury
Next generation sequencing
Descripción
Sumario:Purpose: The etiopathogenesis of drug-induced liver injury (DILI) is still far from being elucidated. This study aims to the study of genetic variations in DILI, related to the drug target, and specifically in the genes coding for the cyclooxygenase enzymes. Methods: By using Next-generation Sequencing we analyzed the genes coding for COX enzymes (PTGS1 and PTGS2) in 113 individuals, 13 of which were patients with DILI caused by COX-inhibitors. Results: The key findings of the study are the increased frequency, among DILI patients, of SNPs causing alterations in transcription factor binding sites and non-synonymous PTGS gene variants, as compared to control subjects. Moreover, the association with non-synonymous SNPs was exclusive of DILI patients with late-onset (50 days or more) Pc