1. Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases.
- Author
-
Bermúdez de León M, León-Cachón RBR, Silva-Ramírez B, González-Ríos RN, Escobedo-Guajardo B, Leyva-Parra R, Tovar-Cisneros B, González-González E, Alvarado-Díaz A, Vázquez-Monsiváis O, Mata-Tijerina V, Puente-Lugo L, Álvarez-Galván E, Currás-Tuala MJ, Aguado-Barrera M, Castorena-Torres F, Alcocer-González JM, Elizondo G, and Salinas-Martínez AM
- Subjects
- Acute Disease, Adolescent, Adult, Antiviral Agents adverse effects, Biological Transport physiology, Child, Drug Interactions physiology, Drug-Related Side Effects and Adverse Reactions epidemiology, Female, Genetic Association Studies methods, Humans, Influenza A Virus, H1N1 Subtype isolation & purification, Influenza, Human drug therapy, Influenza, Human epidemiology, Influenza, Human genetics, Influenza, Human metabolism, Male, Mexico epidemiology, Middle Aged, Oseltamivir adverse effects, Protein Transport physiology, Respiration Disorders drug therapy, Respiration Disorders epidemiology, Retrospective Studies, Young Adult, Antiviral Agents metabolism, Drug-Related Side Effects and Adverse Reactions genetics, Drug-Related Side Effects and Adverse Reactions metabolism, Oseltamivir metabolism, Polymorphism, Single Nucleotide genetics, Respiration Disorders genetics, Respiration Disorders metabolism
- Abstract
Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy-Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.
- Published
- 2020
- Full Text
- View/download PDF