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.
AIM: Approximately a third of newly diagnosed epilepsypatients 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 epilepsypatients from Malaysia and Hong Kong who were receiving AEDs. Meta-analysis was performed for pooled data of SCN1Ars3812718 and rs2298771, and SCN2Ars17183814 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 SCN1Ars3812718 and rs2298771, and for SCN2Ars17183814 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.
Authors: Larry Baum; Batoul Sadat Haerian; Ho-Keung Ng; Virginia C N Wong; Ping Wing Ng; Colin H T Lui; Ngai Chuen Sin; Chunbo Zhang; Brian Tomlinson; Gary Wing-Kin Wong; Hui Jan Tan; Azman Ali Raymond; Zahurin Mohamed; Patrick Kwan Journal: Hum Genet Date: 2013-12-13 Impact factor: 4.132