SCN1A, SCN2A and SCN3A Gene Polymorphisms and Responsiveness to Antiepileptic Drugs: A Multicenter Cohort Study and Meta-Analysis

Abstract

Aim: Approximately a third of newly diagnosed epilepsy patients do not respond to antiepileptic drugs (AEDs). Evidence suggests that low penetrance variants in the genes of drug targets such as voltage-gated sodium channels may be involved in drug responsiveness. To examine this hypothesis, we compared data from two epilepsy cohorts from Malaysia and Hong Kong, as well as a meta-analysis from published data. Materials & methods: Genotype analysis of 39 polymorphisms located in the SCN1A, SCN2A and SCN3A genes was performed on 1504 epilepsy patients from Malaysia and Hong Kong who were receiving AEDs. Meta-analysis was performed for pooled data of SCN1A rs3812718 and rs2298771, and SCN2A rs17183814 polymorphisms. Results: Our data from the Hong Kong and Malaysia cohorts showed no significant allele, genotype and haplotype association of polymorphisms in the SCN1A, SCN2A, and SCN3A genes with drug responsiveness in epilepsy. This finding was supported by a meta-analysis for SCN1A rs3812718 and rs2298771, and for SCN2A rs17183814 polymorphisms. Conclusion: Our comprehensive study suggests that common polymorphisms in SCN1A, SCN2A and SCN3A do not play major roles in influencing response to AEDs.

Original submitted 11 March 2013; Revision submitted 31 May 2013

KEYWORDS::

• drug responsiveness
• epilepsy
• polymorphism
• SCN1A
• SCN2A
• SCN3A

Financial & competing interests disclosure

This study was supported by Malaysian Grant HIR MOHE E000025-20001 and Research Grants Council of the Hong Kong Special Administrative Region, China, Project no. HKU7623/08M, HKU7747/07M and CUHK4466/06M. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by Malaysian Grant HIR MOHE E000025-20001 and Research Grants Council of the Hong Kong Special Administrative Region, China, Project no. HKU7623/08M, HKU7747/07M and CUHK4466/06M. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.