2026-06-01T11:58:26Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/292842026-02-03T11:28:26Zcom_10630_2254col_10630_37953

Genetic polymorphisms of CYP2C9 and CYP2C19 are not related to drug-induced idiosyncratic liver injury (DILI) Pachkoria, K. Lucena-González, María Isabel Ruiz-Cabello, Francisco Crespo, Esperanza Cabello-Porras, María Rosario Andrade-Bellido, Raúl Jesús Toxicología Background and purpose: The general view on the pathogenesis of drug-induced idiosyncratic liver injury (DILI) is that parent compounds are rendered hepatotoxic by metabolism, mainly by cytochrome (CYP) 450, although other metabolic pathways can contribute. Anecdotal reports suggest a role of CYP 450 polymorphisms in DILI. We aimed to assess in a series of Spanish DILI patients the prevalence of important allelic variants of CYP2C9 and CYP2C19, known to be involved in the metabolism of several hepatotoxic drugs. Experimental approach: Genotyping of CYP2C9 ((*)2, (*)3) and CYP2C19 ((*)2 and (*)3), was carried out in a total of 28 and 32 patients with a well established diagnosis of DILI. CYP2C9 and CYP2C19 variants were analysed in genomic DNA by means of PCR-FRET and compared with previous findings in other Caucasian populations. Key results: CYP2C9 and CYP2C19 allele and genotype frequencies were in agreement with Hardy-Weinberg equilibrium. Fourteen patients (50%) were heterozygous and 1(4%) found to be compound heterozygous for the CYP2C9 allele. Seven (22%) were found to carry one and 1(3%) carried two CYP2C19 mutated alleles. No patients were homozygous for (*)3 allele. The distribution of both CYP2C9 and CYP2C19 allelic variants in DILI patients were similar to those in other Caucasian populations. Patients with variant and those with wild-type alleles did not differ in regard to clinical presentation of DILI, type of injury and outcome. Conclusions and implications: We find no evidence to support CYP2C9 and CYP2C19 genetic polymorphisms as predictable potential risk factors for DILI. 2024-01-26T10:48:26Z 2024-01-26T10:48:26Z 2007-01-29 journal article Pachkoria, K., Lucena, M.I., Ruiz-Cabello, F., Crespo, E., Cabello, M.R., Andrade, R.J. and (2007), Genetic polymorphisms of CYP2C9 and CYP2C19 are not related to drug-induced idiosyncratic liver injury (DILI). British Journal of Pharmacology, 150: 808-815. https://doi.org/10.1038/sj.bjp.0707122 https://hdl.handle.net/10630/29284 10.1038/sj.bjp.0707122 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional