RT Journal Article
T1 Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort.
A1 Ulzurrun, Eugenia
A1 Stephens, Camilla
A1 Ruiz-Cabello, Francisco
A1 Robles-Díaz, Mercedes
A1 Sáenz-López, Pablo
A1 Hallal, Hacibe
A1 Soriano, Germán
A1 Román, Eva
A1 Fernández, M Carmen
A1 Lucena, M Isabel
A1 Andrade, Raúl J
K1 Alelos
K1 Polimorfismo Genético
K1 Transportadoras de Casetes de Unión a ATP
K1 Proteínas Asociadas a Resistencia a Múltiples Medicamentos
K1 Enfermedad Hepática Inducida por Drogas
K1 Haplotipos
K1 España
K1 Bilirrubina
K1 Estudios Epidemiológicos
AB BACKGROUND AND AIMSFlawed 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.METHODSA total of ten polymorphisms 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.RESULTSNone 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.CONCLUSIONSOur 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.
PB Public Library of Science
YR 2014
FD 2014-04-14
LK http://hdl.handle.net/10668/1628
UL http://hdl.handle.net/10668/1628
LA en
NO Ulzurrun E, Stephens C, Ruiz-Cabello F, Robles-Díaz M, Sáenz-López P, Hallal H, et al. Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort. PLoS ONE. 2014; 9(4):e94675
NO Journal Article;
DS RISalud
RD Jul 30, 2025