Selected ABCB1, ABCB4 and ABCC2 Polymorphisms Do Not Enhance the Risk of Drug-Induced Hepatotoxicity in a Spanish Cohort
Ulzurrun, Eugenia (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Stephens, Camilla (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Ruiz-Cabello, Francisco (Instituto de Investigación Sanitaria de Granada)
Robles-Diaz, Mercedes (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Saenz-López, Pablo (Universidad de Granada)
Hallal, Hacibe (Hospital General Universitario Morales Meseguer (Múrcia))
Soriano, German (Institut d'Investigació Biomèdica Sant Pau)
Roman, Eva (Institut d'Investigació Biomèdica Sant Pau)
Fernandez, M. Carmen (Complejo Hospitalario Torrecárdenas (Almeria))
Lucena, M. Isabel (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Andrade, Raúl J. (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Universitat Autònoma de Barcelona

Date:	2014
Abstract:	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. A 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. 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. 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.
Grants:	Instituto de Salud Carlos III PS09/01384
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 9 (april 2014) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0094675
PMID: 24732756

8 p, 341.4 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles