Abstract
BackgroundMany antiseizure medications (ASMs) control seizures by blocking voltage-dependent sodium channels. Polymorphisms of sodium channel genes may affect the response to ASMs due to altering the effect of ASMs on blocking sodium channels.MethodsWe conducted a retrospective study of epilepsy patients followed up at the Neurological Department of Kaohsiung Chang Gung Memorial Hospital, Taiwan between January 2010 and December 2018. We categorized the patients into response, partial response, and failure to sodium channel blocking ASM groups. Sodium channel blocking ASMs included phenytoin, carbamazepine, lamotrigine, oxcarbazepine, lacosamide, zonisamide, topiramate, and valproic acid. A subgroup of predominant sodium channel blocking ASMs included phenytoin, carbamazepine, lamotrigine, oxcarbazepine, and lacosamide. Associations between the response of ASMs and single-nucleotide polymorphisms of SCN1A, SCN1B, SCN2A, and SCN9A were analyzed.ResultsTwo hundred Taiwanese patients and 21 single-nucleotide polymorphisms among SCN1A, SCN1B, SCN2A, and SCN9A were evaluated. We found allele C of rs55742440 in SCN1B was statistically significantly associated with not achieving seizure-free with sodium channel blocking ASMs. For the predominant sodium channel blocking ASMs group, no SNPs were associated with the response of ASMs.ConclusionSingle-nucleotide polymorphism in SCN1B was associated with the response to sodium channel blocking ASMs. This highlights the possibility that beta subunits may affect the function of sodium channels and resulted in different responsiveness to ASMs.
Highlights
Many antiseizure medications (ASMs) control seizures by blocking voltage-dependent sodium channels
We evaluated the efficacy of the ASMs according to the seizure frequency after adding the last Sodium channel (SCN)-ASM and categorized the efficacy according to the International League Against Epilepsy (ILAE) consensus [3]
The clinical characteristics of patients not achieving seizure-free to SCN-ASMs (n = 91) were shown in Table 2, which were categorized into having partial response and failure
Summary
Many antiseizure medications (ASMs) control seizures by blocking voltage-dependent sodium channels. Several theories tried to explain the cause of drug-resistant epilepsy, including the transporter hypothesis [4], the neuronal network hypothesis [5], the intrinsic severity hypothesis [6], the target hypothesis [7], and the gene variant hypothesis [8] Among these theories, we focused on the gene variant hypothesis, which is the pharmacogenetic association of the responsiveness of ASM and the genetic variant of ASM targets. Tate et al reported that the SCN1A rs3812718 variant was associated with the maximum dose of phenytoin and carbamazepine for controlling seizures [11] This SNP has been reported to be related to drug-resistant epilepsy in different ethnic groups [12,13,14] but with conflicting results [15,16,17]. A recent study evaluated 39 polymorphisms in the SCN1A, SCN2A, and SCN3A genes in patients from Malaysia and Hong Kong, had found no associations between gene polymorphisms and responsiveness to ASMs [21]
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