Genetic polymorphisms of CYP2C9 and CYP2C19 are not related to drug‐induced idiosyncratic liver injury (DILI)
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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.
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Genetic polymorphisms in CYP2C9 have not been shown to significantly contribute to DILI risk.
“The role of CYP2C9, the enzyme responsible for the formation of SMX-HA, has been studied in relation to DILI, and genetic polymorphisms in CYP2C9 have not been shown to significantly contribute to DILI risk.31,32”
From N-Acetyltransferase (NAT) 1 and NAT2 Enzyme Activities Drive Interindividual Variability in Sulfamethoxazole N-Acetylation (2025) · cites this paper as [31]
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References 42 · Cited by 49
- Authors
- Pachkoria, K., Lucena, M. I., Ruiz‐Cabello, F., Crespo, E., Cabello, M. R., Andrade, R. J., & on behalf of the Spanish Group for the Study of Drug‐Induced Liver Disease (Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos (GEHAM)
- Affiliations
- Hospital Clínico Universitario Virgen de la Victoria (ES)
- Hospital Universitario Virgen de las Nieves (ES)
- Universidad de Granada (ES)
- Corresponding author
- Lucena, M I
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2007-03
- Volume
- 150
- Issue
- 6
- Pages
- 808-815
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2013859
- OpenAlex
- W2095346514
- Cited by
- 49
- References
- 42
- Citations by year
- 2025: 2 · 2023: 2 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 8 · 2012: 6
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Repositorio Institucional de la Universidad de Málaga (University of Málaga) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Keywords
- CYP2C9, CYP2C19, genetic polymorphism, cytochrome P450, hepatotoxicity, allele frequency, compound heterozygosity, genetic risk factors, drug metabolism
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Aryl Hydrocarbon Hydroxylases, Female, Gene Frequency, Humans, Mixed Function Oxygenases, Liver, Male, Middle Aged, Risk Factors, Spain, Genetic Variation, Polymorphism, Single Nucleotide, Chemical and Drug Induced Liver Injury, Cytochrome P-450 CYP2C9, Cytochrome P-450 CYP2C19
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