The Role of Candidate Pharmacogenetic Variants in Determining Valproic Acid Efficacy, Toxicity, and Concentrations in Patients with Epilepsy

    October 2024 in “ Frontiers in Pharmacology ”
    Hady Yazbeck, Joe Youssef, Wassim Nasreddine, Abdallah Kurdi, Nathalie K. Zgheib, Ahmad Beydoun
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    TLDR Genetic variants can affect valproic acid's effectiveness, side effects, and levels in epilepsy treatment.
    This study examines the influence of pharmacogenetic variants on the efficacy, toxicity, and serum concentrations of valproic acid (VPA) in 3,010 epilepsy patients, with a focus on genetic generalized epilepsies. Whole exome sequencing of 1,238 samples identified significant single nucleotide polymorphisms (SNPs) affecting treatment outcomes. Key findings include the rs3892097 (CYP2D6) variant's association with increased treatment failure, the rs1137101 (LEPR) variant's link to hair loss and weight gain, and the rs4880 (SOD2) variant's protective effect against hair loss. The rs1057910 (CYP2C9*3) variant correlates with higher VPA concentrations. These results underscore the potential of pharmacogenetics in optimizing epilepsy treatment, though further validation is needed due to genetic complexity.
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