Genetyczne warianty CYP2C9 i niepożądane działania leków przeciwpadaczkowych: analiza wstępna w Andach Wenezueli
<em>CYP2C9</em> Pharmacogenetic Variants and Adverse Drug Reactions to Antiseizure Medications: An Exploratory Analysis in the Venezuelan Andes
W skrócie
[Preprint - wstępne wyniki] Badanie wykazało, że genetyczne warianty CYP2C9 wpływają na bezpieczeństwo leków przeciwpadaczkowych u pacjentów z Andów Wenezueli - osoby o wolniejszym metabolizmie (słabi metabolizatorzy) miały 16 razy wyższe ryzyko niepożądanych działań leków niż osoby z normalnym metabolizmem. Ryzyko niepożądanych działań było również znacznie wyższe u pacjentów przyjmujących wiele leków jednocześnie w porównaniu z pacjentami na jednym leku.
Oryginalny abstract (angielski)
Background: /Objectives: Epilepsy is a chronic neurological disorder affecting more than 50 million people worldwide. All antiseizure medications may cause adverse drug reac-tions (ADRs), including neurological, cognitive, mood-related, and systemic manifesta-tions. In Venezuela, epilepsy represents a public health challenge due to the lack of epi-demiological and pharmacogenetic data. This study evaluated the association between the CYP2C9*2 and CYP2C9*3 variants and the incidence of adverse drug reactions in patients receiving antiseizure therapy in the Venezuelan Andean region. Methods: An observa-tional, descriptive, and cross-sectional study in 72 patients, was conducted. Genomic DNA was extracted from venous blood samples, and genotypes were determined by re-al-time polymerase chain reaction (PCR) using TaqMan® probes for allelic discrimination. Results: The observed allele frequencies were 0.15 for CYP2C9*2 and 0.06 for CYP2C9*3. Patients with intermediate and poor metabolizer phenotypes exhibited a significantly higher risk of developing ADRs compared with normal metabolizers (OR = 16.33; 95% CI: 4.30–62.01; p < 0.001). Likewise, polytherapy markedly increased the risk of ADRs com-pared with monotherapy (OR = 25.71; 95% CI: 2.60–254.03; p = 0.005). Conclusion: The CYP2C9*2 and CYP2C9*3 variants may influence the safety of antisei-zure therapy in patients from the Venezuelan Andes by determining intermediate and poor metabolizer phenotypes and thereby affecting the pharmacokinetics of these medica-tions, as previously reported in international studies.