Background: Epilepsy is one of the most common central nervous system pediatric diseases. About 20-30% of patients do not respond to antiepileptic drugs (AEDs) despite an appropriate pharmacological approach. Many antiepileptic drugs prevent seizures blocking neural voltage-gated sodium channels. In this study, we evaluated the association between four single-nucleotide polymorphisms (SNPs) of the sodium channel alpha gene (SCN1A) and drug-resistance in epileptic children. Methods: We enrolled 105 epileptic patients, including 56 drug-responsive and 49 drug-resistant subjects. We investigated four polymorphic regions, rs6730344A/C, rs6432858C/T, rs11690962G/T and rs12614431A/G, within the SCN1A gene. Genotyping of SNPs was carried out by PCR-RFLP. Results: Our results demonstrated a statistically significant difference in rs6730344A/C, rs6432858C/T, rs11690962G/T genotypic distribution between resistant and responsive patients (p<0.006). CC genotype of rs6730344A/C, CC genotype of rs6432858C/T and GG genotype of rs11690962G/T were associated with drug-resistance (O.R.=1.6, 95% C.I. 1.4-2.7; O.R.=2.13, 95% C.I. 1.2-3.5; O.R.=1.7, 95% C.I. 1.1-2.7, respectively). There was no association between rs12614431A/G genotypic variants and drug-resistance. Conclusions: Our results suggest that rs6730344A/C, rs6432858C/T and rs11690962G/T might be risk factors for refractory epilepsy. These data must to be confirmed by further studies.
Association of SCN1A gene polymorphysms with Childhood Refractory Epilepsy
FUMARULO, Ruggiero;MARGARI, Lucia
2014-01-01
Abstract
Background: Epilepsy is one of the most common central nervous system pediatric diseases. About 20-30% of patients do not respond to antiepileptic drugs (AEDs) despite an appropriate pharmacological approach. Many antiepileptic drugs prevent seizures blocking neural voltage-gated sodium channels. In this study, we evaluated the association between four single-nucleotide polymorphisms (SNPs) of the sodium channel alpha gene (SCN1A) and drug-resistance in epileptic children. Methods: We enrolled 105 epileptic patients, including 56 drug-responsive and 49 drug-resistant subjects. We investigated four polymorphic regions, rs6730344A/C, rs6432858C/T, rs11690962G/T and rs12614431A/G, within the SCN1A gene. Genotyping of SNPs was carried out by PCR-RFLP. Results: Our results demonstrated a statistically significant difference in rs6730344A/C, rs6432858C/T, rs11690962G/T genotypic distribution between resistant and responsive patients (p<0.006). CC genotype of rs6730344A/C, CC genotype of rs6432858C/T and GG genotype of rs11690962G/T were associated with drug-resistance (O.R.=1.6, 95% C.I. 1.4-2.7; O.R.=2.13, 95% C.I. 1.2-3.5; O.R.=1.7, 95% C.I. 1.1-2.7, respectively). There was no association between rs12614431A/G genotypic variants and drug-resistance. Conclusions: Our results suggest that rs6730344A/C, rs6432858C/T and rs11690962G/T might be risk factors for refractory epilepsy. These data must to be confirmed by further studies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
