2026-06-03T14:36:51Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/297552026-02-03T10:58:10Zcom_10630_2254col_10630_37953

Role of chemical structures and the 1331T>C bile salt export pump polymorphism in idiosyncratic drug-induced liver injury Ulzurrun, Eugenia Stephens, Camilla Crespo, Esperanza Ruiz-Cabello, Francisco Ruiz-Nuñez, Julia Saenz-López, Pablo Moreno-Herrera, Inmaculada Robles-Díaz, María Mercedes Hallal, Hacibe Moreno-Planas, José María Cabello-Porras, María Rosario Lucena-González, María Isabel Andrade-Bellido, Raúl Jesús Hígado - Efectos de los medicamentos Farmacogenética Background & aims: Several pharmaceutical compounds have been shown to exert inhibitory effects on the bile salt export pump (BSEP) encoded by the ABCB11 gene. We analysed the combined effect on drug-induced liver injury (DILI) development of the ABCB11 1331T>C polymorphism and the presence of specific chemical moieties, with known BSEP inhibiting properties, in the causative drug. Methods: Genotyping using a TaqMan 5' allelic discrimination assay was performed in 188 Spanish DILI patients, 219 healthy controls and 91 sex-, age- and drug-matched controls. A chemical structure analysis was performed for each individual causative drug. Results: The CC genotype was significantly associated with hepatocellular damage [odds ratio (OR) = 2.1, P = 0.001], particularly in NSAID DILI cases (OR = 3.4, P = 0.007). In addition, the CC genotype was found to be significantly linked to DILI development from drugs causing <50% BSEP inhibition (OR = 1.8, Pc = 0.011). Of the BSEP inhibitory chemical moieties, 59% of the causative drugs contained a carbocyclic system with at least one aromatic ring, corresponding to 61% of the total cases. The C allele was significantly more frequent in DILI cases containing this chemical moiety, which appear to be conditioned on the ABCB11 1331T>C polymorphism in the absence of other BSEP inhibitory structures. Conclusion: Patients carrying the C allele in the ABCB11 1331T>C polymorphism are at increased risk of developing hepatocellular type of DILI, when taking drugs containing a carbocyclic system with aromatic rings. 2024-02-05T08:28:34Z 2024-02-05T08:28:34Z 2013-04 journal article https://hdl.handle.net/10630/29755 doi.org/10.1111/liv.12193 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional WILEY