Polymorphisms in the Voltage-gated Sodium Channel Genes and Antiepileptic Efficacy of Carbamazepine

J Korean Neurol Assoc > Volume 27(2); 2009 > Article

Journal of the Korean Neurological Association 2009;27(2): 147-153.

소디움채널 유전자변이와 카바마제핀의 항경련효과

장신영, 김명규 남태승 김준태 최성민 이승한 박만석 김병채 조기현

전남대학교 의과대학 신경과학교실, 전남대학교 의생명인력사업단a

Polymorphisms in the Voltage-gated Sodium Channel Genes and Antiepileptic Efficacy of Carbamazepine

Sin-Young Jang

Deptment of Neurology, Chonnam National University Medical School, The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National Universitya, Gwangju, Korea

Abstract

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. Key Words: Epilepsy, Sodium channels, Carbamazepine, Drug resistance, Single-nucleotide polymorphism