2026-04-29T15:24:44Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/170652024-11-28T14:43:34Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16959
Repisalud
author
Ulzurrun, Eugenia
author
Stephens, Camilla
author
Ruiz-Cabello, Francisco
author
Robles-Díaz, Mercedes
author
Sáenz-López, Pablo
author
Hallal, Hacibe
author
Soriano, Germán
author
Román, Eva
author
Fernández, M Carmen
author
Lucena, M Isabel
author
Andrade, Raúl J
authoraffiliation
[Ulzurrun,E; Stephens,C; Robles-Díaz,M; Lucena,MI; Andrade, RJ] S Farmacología Clínica and UGC de Gastroenterología y Hepatología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Spain. [Ulzurrun,E; Stephens,C; Robles-Díaz,M; Soriano,G; Román,E; Lucena,MI; Andrade; RJ] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. [Ruiz-Cabello,F; Sáenz-López,P] Departamento de Bioquímica y Biología Molecular III/Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Spain. [Ruiz-Cabello,F] Instituto de Investigación Biosanitario de Granada, Spain. [Hallal,H] Servicio de Aparato Digestivo, Hospital Morales Meseguer, Murcia, Spain. [Soriano,G; Román,E] Servicio de Gastroenterología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain. [Román,E] Escola Universitària d'Infermeria EUI-Sant Pau, Universitat Autònoma de Barcelona, Spain. [Fernández,MC] Unidad de Gestión Clínica de Farmacia, Hospital Torrecárdenas, Almería, Spain.
2024-01-15T18:17:12Z
2024-01-15T18:17:12Z
2014-04-14
10.1371/journal.pone.0094675
1932-6203
PloS One
http://hdl.handle.net/10668/1628
24732756
http://hdl.handle.net/20.500.12105/17065
BACKGROUND AND AIMS: Flawed ABC transporter functions may contribute to increased risk of drug-induced liver injury (DILI). We aimed to analyse the influence of genetic variations in ABC transporters on the risk of DILI development and clinical presentations in a large Spanish DILI cohort. METHODS: A total of ten polmorphisms in ABCB1 (1236T>C, 2677G>T,A, 3435T>C), ABCB4 (1954A>G) and ABCC2 (-1774G>del, -1549A>G, -24C>T, 1249G>A, 3972C>T and 4544G>A) were genotyped using Taqman 5' allelic discrimination assays or sequencing in 141 Spanish DILI patients and 161 controls. The influence of specific genotypes, alleles and haplotypes on the risk of DILI development and clinical presentations was analysed. RESULTS: None of the individual polymorphisms or haplotypes was found to be associated with DILI development. Carriers homozygous for the ABCC2 -1774del allele were however only found in DILI patients. Hence, this genotype could potentially be associated with increased risk, though its low frequency in our Spanish cohort prevented a final conclusion. Furthermore, carriers homozygous for the ABCC2 -1774G/-1549A/-24T/1249G/3972T/4544G haplotype were found to have a higher propensity for total bilirubin elevations when developing DILI. CONCLUSIONS: Our findings do not support a role for the analysed polymorphisms in the ABCB1, ABCB4 and ABCC2 transporter genes in DILI development in Spanish patients. The ABCC2 -1774deldel genotype was however restricted to DILI cases and could potentially contribute to enhanced DILI susceptibility.
eng
Alelos
Polimorfismo Genético
Transportadoras de Casetes de Unión a ATP
Proteínas Asociadas a Resistencia a Múltiples Medicamentos
Enfermedad Hepática Inducida por Drogas
Haplotipos
España
Bilirrubina
Estudios Epidemiológicos
Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort.
research article