Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases

Autor: Rosa Nelly González-Ríos, Ana María Salinas-Martínez, Brenda L. Escobedo-Guajardo, María José Currás-Tuala, Everardo González-González, Ofelia Vázquez-Monsiváis, Mario Bermúdez de León, Miguel E. Aguado-Barrera, Benjamín Tovar-Cisneros, Viviana L. Mata-Tijerina, Juan Manuel Alcocer-González, Erick Álvarez-Galván, Rafael B. R. León-Cachón, Guillermo Elizondo, Lorena Puente-Lugo, Abdiel Alvarado-Díaz, Roberto Leyva-Parra, Beatriz Silva-Ramírez, Fabiola Castorena-Torres
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
030226 pharmacology & pharmacy
law.invention
chemistry.chemical_compound
0302 clinical medicine
Influenza A Virus
H1N1 Subtype
law
Medicine
Drug Interactions
Child
Polymerase chain reaction
virus diseases
Middle Aged
Protein Transport
Chemoprophylaxis
Acute Disease
Molecular Medicine
Female
Gastritis
medicine.symptom
Adult
medicine.medical_specialty
Oseltamivir
Adolescent
Drug-Related Side Effects and Adverse Reactions
Single-nucleotide polymorphism
Predictive markers
Antiviral Agents
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
Young Adult
Internal medicine
Genetic model
Influenza
Human
Genetics
Humans
Allele
Genotyping
Mexico
Genetic Association Studies
Retrospective Studies
Pharmacology
business.industry
Biological Transport
Respiration Disorders
030104 developmental biology
chemistry
Genetic markers
business
Zdroj: The Pharmacogenomics Journal
ISSN: 1473-1150
1470-269X
Popis: 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.
Databáze: OpenAIRE
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