Abstracts

Rationale: Mutations in voltage-gated sodium channel genes, including SCN1A, SCN2A, and SCN1B, can cause certain forms of idiopathic epilepsy. However, genetic association of these genes with non-idiopathic epilepsy has not been reported. Methods: The relevant institutional research ethics committees approved this multicenter study. All subjects or their parents/legal guardians gave written informed consent. In order to investigate whether common variants in voltage-gated sodium channel genes affect epilepsy risk, we genotyped 490 epilepsy patients and 136 control subjects, all Hong Kong Chinese, for SNPs in five genes. The Tagger function of Haploview software was used to select 28 tagging SNPs in SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B, capturing at least 75% of HapMap alleles (with minor allele frequency >= 5%) at r²>=0.8. Results: Alleles of SNPs in SCN2A and 3A were associated with epilepsy at p<0.05, with the strongest association being rs7592445 (in SCN2A), at p=0.007, odds ratio 1.5 for the C allele. Alleles of SCN2B were associated with epilepsy, with the strongest association being rs602594 at p=0.02, odds ratio 1.6 for the T allele. For rs7592445, p=0.1, odds ratio 1.5 for idiopathic epilepsy and p=0.006, odds ratio 1.6 for non-idiopathic epilepsy. For rs602594, p=0.8, odds ratio 1.1 for idiopathic epilepsy and p=0.01, odds ratio 1.6 for non-idiopathic epilepsy. Conclusions: Common variants in voltage-gated sodium channel genes may affect risk of developing epilepsy, including non-idiopathic epilepsy. Funding: Hong Kong Research Grants Council Clinical Research Fellowship Grant (CERG Project CUHK4466/06M).