SCN1A IVS5N+5 Polymorphism and Response to Sodium Valproate: A Multicenter Study

Abstract

Aim: Approximately 30% of epilepsy patients do not response to antiepileptic drugs (AEDs). The functional SCN1A IVS5N+5 polymorphism may play a role in response to some AEDs. The purpose of this study was to examine this hypothesis in a cohort study of Malaysian and Hong Kong Chinese epilepsy patients on sodium valproate (VPA) monotherapy and in a meta-analysis. Patients & methods: The SCN1A IVS5N+5 polymorphism was genotyped in 583 Malaysian (84%) and Hong Kong Chinese (16%) epilepsy patients receiving VPA monotherapy. The related association studies, including the current study, were meta-analyzed by using fixed- and random-effects models under various genetic models. Results: A total of 277 (47.5%) and 306 (52.5%) patients were VPA nonresponsive and responsive, respectively. Unlike Chinese and Indian patients, Malay nonresponsive patients with idiopathic generalized epilepsy showed significant association, probably caused by the small sample size. Conclusion: The cohort study and meta-analysis did not demonstrate an association between AED responsiveness and this polymorphism. Future studies with a larger sample size of Malays with idiopathic generalized epilepsy are suggested.

Original submitted 15 June 2012; Revision submitted 23 July 2012

KEYWORDS::

• alternative splicing
• epilepsy
• meta-analysis
• polymorphism
• SCN1A
• sodium valproate

Acknowledgements

The authors gratefully acknowledge the Malaysian and Hong Kong Chinese patients for their participation in this study, as well as the staff of the hospitals for their assistance in recruiting patients.

Financial & competing interests disclosure

This work was supported by Grant HIR MOHE E000025-20001 and Research Grants Council of the Hong Kong Special Administrative Region, China (Project no. 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 work was supported by Grant HIR MOHE E000025-20001 and Research Grants Council of the Hong Kong Special Administrative Region, China (Project no. 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.