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KMID : 0359720090270020147
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Journal of the Korean Neurological Association
2009 Volume.27 No. 2 p.147 ~ p.153
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Polymorphisms in the Voltage-gated Sodium Channel Genes and Antiepileptic Efficacy of Carbamazepine
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Jang Sin-Young
Nam Tai-Seung
Park Man-Seok
Cho Ki-Hyun
Choi Seong-Min
Lee Seung-Han
Kim Byeong-Chae
Kim Joon-Tae
Kim Myeong-Kyu
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Abstract
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Background: Voltage-gated sodium channels are responsible for the initial-depolarization component of action potentials in brain neurons, and hence they are the target for widely used antiepileptic drugs such as carbamazepine (CBZ). With the working hypothesis that genetic defect in voltage-gated sodium channels can alter the response to CBZ, this study was performed to elucidate the relationship between single-nucleotide polymorphisms (SNPs) of the SCN1A, SCN1B, and SCN2A genes and CBZ resistance in Korean epileptics.
Methods: Candidate SNPs of SCN1A, SCN1B, and SCN2A were developed using the pooled DNA from healthy controls (n=200), of which representative SNPs of each of SCN1A, SCN1B, and SCN2A were determined based on theoretical functional values. Each representative SNP was genotyped for a CBZ-resistant group (CRE, n=168) and a CBZ- responsive group (CSE, n=154), and the frequencies of alleles and genotypes of each SNP were compared between the two groups.
Results: Eighteen SNPs were developed in SCN1A, SCN1B, and SCN2A. SCN1A-PM in exon 16 of SCN1A, SCN1B-PM in exon 3 of a splicing variant of SCN1B, and SCN2A-PM in the 7th intronic sequence of SCN2A were selected as the representative SNPs for these genes. The distributions of alleles and genotypes of each representative SNP did not differ between the CRE and CSE groups.
Conclusions: In Korean epileptics, there appears to be no significant relationship between representative SNPs of SCN1A, SCN1B, and SCN2A and CBZ resistance.
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KEYWORD
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Epilepsy, Sodium channels, Carbamazepine, Drug resistance, Single-nucleotide polymorphism
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