{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:57:37Z","timestamp":1790675857737,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u00ae 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\u201376.56; p &lt; 0.001) and in patients on polypharmacy (OR = 15.03; 95%CI: 2.73\u2013157.37; 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.<\/jats:p>","DOI":"10.3390\/ijms27198690","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:10:54Z","timestamp":1790673054000},"page":"8690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CYP2C9 Pharmacogenetic Variants and Adverse Drug Reactions to Antiseizure Medications: An Exploratory Analysis in the Venezuelan Andes"],"prefix":"10.3390","volume":"27","author":[{"given":"Alexis","family":"Morales-Ortiz","sequence":"first","affiliation":[{"name":"Department of Toxicology and Pharmacology, Faculty of Pharmacy and Bioanalysis, University of Los Andes, M\u00e9rida 5101, Venezuela"},{"name":"Laboratory 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7967-5320","authenticated-orcid":false,"given":"Luis Abel","family":"Qui\u00f1ones","sequence":"additional","affiliation":[{"name":"Laboratory 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1000-1667","authenticated-orcid":false,"given":"Sol Betzabeth","family":"Rond\u00f3n-Simancas","sequence":"additional","affiliation":[{"name":"Neurology Unit, Faculty of Medicine, University of Los Andes, M\u00e9rida 5101, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Paredes","sequence":"additional","affiliation":[{"name":"Neurology Unit, Faculty of Medicine, University of Los Andes, M\u00e9rida 5101, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Avenda\u00f1o","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Paediatrics and Child Care, Faculty of Medicine, University of Los Andes, M\u00e9rida 5101, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3637-9677","authenticated-orcid":false,"given":"Zaida","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Pharmacology, Faculty of Pharmacy and Bioanalysis, University of Los Andes, M\u00e9rida 5101, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8717-4307","authenticated-orcid":false,"given":"Haydee","family":"Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University, Ica 11001, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Palomino-Jhong","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University, Ica 11001, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda R.","family":"Bendez\u00fa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University, Ica 11001, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge A.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University, Ica 11001, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Melgar-Merino","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University, Ica 11001, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pompeyo A.","family":"Cuba-Garcia","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University, Ica 11001, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Laos-Anchante","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University, Ica 11001, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina Eliades","family":"Yarasca-Carlos","sequence":"additional","affiliation":[{"name":"Biological Sciences Faculty, San Luis Gonzaga National University, Ica 11001, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Santiago","family":"Almeida-Galindo","sequence":"additional","affiliation":[{"name":"Faculty of Human Medicine, San Luis Gonzaga National University, Ica 11001, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Pariona-Llanos","sequence":"additional","affiliation":[{"name":"Biotechnology, Faculty of Environmental Engineering, University of Applied Sciences, Lima 15067, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe L.","family":"Ignacio-Cconchoy","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Alberto Sabogal National Hospital, Sologuren, Callao 07000, Peru"},{"name":"Centre for Research in Molecular Pharmacology and 4P Medicine, Vice-Rectorate for Research, San Ignacio de Loyola University, La Molina, Lima 15024, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6577-4965","authenticated-orcid":false,"given":"Alvaro E.","family":"Magui\u00f1a-Ignacio","sequence":"additional","affiliation":[{"name":"Centre for Research in Molecular Pharmacology and 4P Medicine, Vice-Rectorate for Research, San Ignacio de Loyola University, La Molina, Lima 15024, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Loja-Herrera","sequence":"additional","affiliation":[{"name":"Centre for Research in Molecular Pharmacology and 4P Medicine, Vice-Rectorate for Research, San Ignacio de Loyola University, La Molina, Lima 15024, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Yaya-Araujo","sequence":"additional","affiliation":[{"name":"Centre for Research in Molecular Pharmacology and 4P Medicine, Vice-Rectorate for Research, San Ignacio de Loyola University, La Molina, Lima 15024, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5229-3007","authenticated-orcid":false,"given":"Nelson M.","family":"Varela","sequence":"additional","affiliation":[{"name":"Laboratory 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel T.","family":"Alvarado","sequence":"additional","affiliation":[{"name":"Centre for Research in Molecular Pharmacology and 4P Medicine, Vice-Rectorate for Research, San Ignacio de Loyola University, La Molina, Lima 15024, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref_1","unstructured":"World 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