RT Journal Article
T1 Role of chemical structures and the 1331T>C bile salt export pump polymorphism in idiosyncratic drug-induced liver injury
A1 Ulzurrun, Eugenia
A1 Stephens, Camilla
A1 Crespo, Esperanza
A1 Ruiz-Cabello, Francisco
A1 Ruiz-Nuñez, Julia
A1 Saenz-López, Pablo
A1 Moreno-Herrera, Inmaculada
A1 Robles-Díaz, María Mercedes
A1 Hallal, Hacibe
A1 Moreno-Planas, José María
A1 Cabello-Porras, María Rosario
A1 Lucena-González, María Isabel
A1 Andrade-Bellido, Raúl Jesús
K1 Hígado -  Efectos de los medicamentos
K1 Farmacogenética
AB 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.
PB WILEY
YR 2013
FD 2013-04
LK https://hdl.handle.net/10630/29755
UL https://hdl.handle.net/10630/29755
LA eng
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026