CYP2C9 Pharmacogenetic Variants and Adverse Drug Reactions to Antiseizure Medications: An Exploratory Analysis in the Venezuelan Andes.
10 affiliations
- 1Department of Toxicology and Pharmacology, Faculty of Pharmacy and Bioanalysis, University of Los Andes, Mérida 5101, Venezuela.
- 2Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Department of Basic and Clinical Oncology, Faculty of Medicine, University of Chile, Santiago de Chile, Chile & Latin American Network for Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF), Santiago 8350499, Chile.
- 3Neurology Unit, Faculty of Medicine, University of Los Andes, Mérida 5101, Venezuela.
- 4Medical Genetics Unit, Department of Paediatrics and Child Care, Faculty of Medicine, University of Los Andes, Mérida 5101, Venezuela.
- 5Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University, Ica 11001, Peru.
- 6Biological Sciences Faculty, San Luis Gonzaga National University, Ica 11001, Peru.
- 7Faculty of Human Medicine, San Luis Gonzaga National University, Ica 11001, Peru.
- 8Biotechnology, Faculty of Environmental Engineering, University of Applied Sciences, Lima 15067, Peru.
- 9Internal Medicine Department, Alberto Sabogal National Hospital, Sologuren, Callao 07000, Peru.
- 10Centre for Research in Molecular Pharmacology and 4P Medicine, Vice-Rectorate for Research, San Ignacio de Loyola University, La Molina, Lima 15024, Peru.
Abstract
Epilepsy is a chronic neurological disorder with a high global prevalence. In Venezuela, the limited availability of epidemiological and pharmacogenetic data represents an important public health challenge. Antiseizure medications (ASMs) are frequently associated with adverse drug reactions (ADRs), which may be influenced by genetic variability in drug-metabolising enzymes. This study evaluated the association between the CYP2C9*2 and CYP2C9*3 variants and the occurrence of ADRs in patients receiving anticonvulsant treatment in the Venezuelan Andes. An observational, analytical, cross-sectional study was conducted in 72 patients. Genomic DNA was extracted from venous blood, and CYP2C9 genotypes were determined by real-time PCR using TaqMan® probes. The frequencies of the CYP2C9*2 and CYP2C9*3 alleles were 0.15 and 0.06, respectively. The metaboliser phenotype was significantly associated with the presence of ADRs. The risk of ADRs was elevated in the intermediate/poor metaboliser group (IM/PM: OR = 17.45; 95%CI: 5.09-76.56; p < 0.001) and in patients on polypharmacy (OR = 15.03; 95%CI: 2.73-157.37; p = 0.001), although this latter estimate showed marked imprecision due to the width of its interval. Consistent with this, the ADR rate was higher in PM (100%; 3/3) and IM (84.2%; 16/19) than in normal group (20.9%; 9/43). In the monotherapy subgroup, the type of ASM showed no association with the occurrence of ADR (p = 0.741). Among normal metabolisers receiving polytherapy, regimens containing valproic acid were associated with the highest proportion of ADRs, with dual therapy including lamotrigine accounting for 28.57%. Although the overall analysis indicated differences in ADR occurrence according to polytherapy regimen (p = 0.043), the limited sample size restricts the strength of these findings. These results suggest that CYP2C9*2 and CYP2C9*3 variants may contribute to variability in the safety of anticonvulsant treatment among patients from the Venezuelan Andes by influencing CYP2C9 metaboliser phenotypes, and consequently, drug pharmacokinetics. Further studies in larger and more representative Venezuelan populations are warranted to validate these findings.
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BibTeX
@article{moralesortiz2026cyp2c9,
title = {{CYP2C9 Pharmacogenetic Variants and Adverse Drug Reactions to Antiseizure Medications: An Exploratory Analysis in the Venezuelan Andes.}},
author = {Alexis Morales-Ortiz and Luis Abel Quiñones and Sol Betzabeth Rondón-Simancas and Gustavo Paredes and Andrea Avendaño and Zaida Gonzalez and Haydee Chávez and Juan J Palomino-Jhong and María R Bendezú and Jorge A García and Elizabeth J Melgar-Merino and Pompeyo A Cuba-Garcia and Doris Laos-Anchante and Paulina Eliades Yarasca-Carlos and José Santiago Almeida-Galindo and Ricardo Pariona-Llanos and Felipe L Ignacio-Cconchoy and Alvaro E Maguiña-Ignacio and Berta Loja-Herrera and Richard Yaya-Araujo and Nelson M Varela and Angel T Alvarado},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198690},
url = {https://europepmc.org/article/MED/42883934},
note = {CC BY},
}
RIS
TY - JOUR
TI - CYP2C9 Pharmacogenetic Variants and Adverse Drug Reactions to Antiseizure Medications: An Exploratory Analysis in the Venezuelan Andes.
AU - Alexis Morales-Ortiz
AU - Luis Abel Quiñones
AU - Sol Betzabeth Rondón-Simancas
AU - Gustavo Paredes
AU - Andrea Avendaño
AU - Zaida Gonzalez
AU - Haydee Chávez
AU - Juan J Palomino-Jhong
AU - María R Bendezú
AU - Jorge A García
AU - Elizabeth J Melgar-Merino
AU - Pompeyo A Cuba-Garcia
AU - Doris Laos-Anchante
AU - Paulina Eliades Yarasca-Carlos
AU - José Santiago Almeida-Galindo
AU - Ricardo Pariona-Llanos
AU - Felipe L Ignacio-Cconchoy
AU - Alvaro E Maguiña-Ignacio
AU - Berta Loja-Herrera
AU - Richard Yaya-Araujo
AU - Nelson M Varela
AU - Angel T Alvarado
PY - 2026
DA - 2026/09/29
JO - International journal of molecular sciences
DO - 10.3390/ijms27198690
UR - https://europepmc.org/article/MED/42883934
AB - Epilepsy is a chronic neurological disorder with a high global prevalence. In Venezuela, the limited availability of epidemiological and pharmacogenetic data represents an important public health challenge. Antiseizure medications (ASMs) are frequently associated with adverse drug reactions (ADRs), which may be influenced by genetic variability in drug-metabolising enzymes. This study evaluated the association between the CYP2C9*2 and CYP2C9*3 variants and the occurrence of ADRs in patients receiving anticonvulsant treatment in the Venezuelan Andes. An observational, analytical, cross-sectional study was conducted in 72 patients. Genomic DNA was extracted from venous blood, and CYP2C9 genotypes were determined by real-time PCR using TaqMan® probes. The frequencies of the CYP2C9*2 and CYP2C9*3 alleles were 0.15 and 0.06, respectively. The metaboliser phenotype was significantly associated with the presence of ADRs. The risk of ADRs was elevated in the intermediate/poor metaboliser group (IM/PM: OR = 17.45; 95%CI: 5.09-76.56; p < 0.001) and in patients on polypharmacy (OR = 15.03; 95%CI: 2.73-157.37; p = 0.001), although this latter estimate showed marked imprecision due to the width of its interval. Consistent with this, the ADR rate was higher in PM (100%; 3/3) and IM (84.2%; 16/19) than in normal group (20.9%; 9/43). In the monotherapy subgroup, the type of ASM showed no association with the occurrence of ADR (p = 0.741). Among normal metabolisers receiving polytherapy, regimens containing valproic acid were associated with the highest proportion of ADRs, with dual therapy including lamotrigine accounting for 28.57%. Although the overall analysis indicated differences in ADR occurrence according to polytherapy regimen (p = 0.043), the limited sample size restricts the strength of these findings. These results suggest that CYP2C9*2 and CYP2C9*3 variants may contribute to variability in the safety of anticonvulsant treatment among patients from the Venezuelan Andes by influencing CYP2C9 metaboliser phenotypes, and consequently, drug pharmacokinetics. Further studies in larger and more representative Venezuelan populations are warranted to validate these findings.
SN - 1422-0067
ER -