Związek między zmianami genetycznymi a skutecznością i działaniami niepożądanymi kwasu walproinowego w dziecięcej epilepsji
Association of polymorphisms with valproic acid efficacy and neurological adverse events in pediatric epilepsy
W skrócie
Badacze sprawdzili, czy określone zmiany genetyczne wpływają na to, jak dobrze lek kwas walproinowy działa u dzieci z epilepsją i jakie powoduje działania niepożądane. Okazało się, że dzieci posiadające konkretny wariant genu wykazywały lepsze wyniki leczenia, mniej napadów i mniej problemów neurologicznych. Wyniki sugerują, że badanie tego wariantu genetycznego mogłoby w przyszłości pomóc w lepszym dostosowaniu leczenia dla każdego dziecka.
Oryginalny abstract (angielski)
OBJECTIVE: Valproic acid (VPA) response in pediatric epilepsy shows high variability. This study investigated the association of tryptophan hydroxylase-2 () polymorphisms with VPA efficacy and adverse drug reactions (ADRs) in children. METHODS: In a retrospective cohort of 199 children with epilepsy receiving VPA treatment, rs4570625 and rs1386494 were genotyped using Sequenom MassArray. Efficacy was categorized as uncontrolled seizure seizure-free. ADRs were systemically recorded, and steady-state VPA concentrations were measured. Network pharmacology integrated protein-protein interactions, and functional enrichment to elucidate 's role in VPA-related neurotoxicity. RESULTS: The rs4570625 polymorphism was significantly associated with VPA treatment outcomes. GG homozygotes exhibited higher seizure-free rates ( = 0.031) and lower incidence of neurological ADRs ( = 0.036). GG carriers also displayed significantly higher VPA serum concentrations. Network pharmacology analyses identified the serotonergic synapse as the dominant enriched pathway linking to VPA neurotoxicity, with and as key regulatory hubs. No significant associations were observed between rs1386494 polymorphism and VPA treatment outcomes. CONCLUSION: rs4570625 may serve as a potential exploratory biomarker for predicting VPA efficacy and neurological toxicity in pediatric epilepsy, mediated through serotonergic pathway dysregulation. Genotype-guided personalization could optimize VPA therapy.