Sekwencjonowanie ukierunkowane i analiza haplotipów genów kanałów potasowych regulowanych napięciem: potencjalny związek z odpowiedzią na leki przeciwpadaczkowe u tureckich pacjentów z epilepsją

Voltage-gated potassium channel genes are among the most frequently implicated in epilepsy and antiseizure medication (ASM) response. In this pilot study, we aimed to identify rare and common variants by sequencing voltage-gated potassium channel (Kv) genes in epilepsy patients using ASM, and to reveal the potential drug responses of these variants. To investigate the role of genetic variants in Kv genes (, , , , , and ) in response to ASMs among 31 epilepsy patients, we used targeted next-generation sequencing (tNGS). Patients were classified as responders or persistent based on seizure control status. Selected variants in the genes were annotated, filtered, and analyzed for association with ASM response. We identified 181 variants in the 6 channel genes, including missense, synonymous, intronic, UTR, and stop-gained variants. Six variants of uncertain significance (VUSs) were observed, including c.*1314C>T, c.*976G>A, (c.2613G>T p.Arg871Ser and c.1148+62T>G), and (c.*6282A>G and c.*2860T>C) Two novel variants were identified in our study group, :c.*1314C>T and :c.*2860T>C. Both were located in the 3' UTR region and classified as VUSs according to ACMG guidelines. In the gene, the CG haplotype comprising rs7029012 and rs10967705 was observed more frequently in patients with drug-persistent epilepsy than in those with drug-responsive epilepsy (18.5% vs. 0.8%; χ = 6.756, = 0.009, BH-FDR = 0.036), suggesting a potential association with pharmacoresistant epilepsy. Our haplotype analysis suggests the potential pharmacogenetic contribution of the gene to ASM response; however, these exploratory findings require validation in larger independent cohorts and functional studies.