The association of SCN1A p.Thr1067Ala polymorphism with epilepsy risk and the response to antiepileptic drugs in Slovenian children and adolescents with epilepsy

Purpose: The voltage-gated sodium channel SCN1A mutations are involved in epileptogenesis and may be associated with different epilepsy phenotypes. The SCN1A channel is also an important antiepileptic drug (AED) target. The aim of this study was to investigate if the SCN1A c.3184A>G/p.Thr1067Ala polymorphism modifies the epilepsy risk or is associated with the responsiveness to AEDs in Slovenian children and adolescents with epilepsy.

Methods: In total, 216 paediatric patients with epilepsy were consecutively recruited during routine outpatient follow-up visits between January 2011 and December 2014. All patients and 95 healthy controls, all Central European Caucasians, were genotyped for the SCN1A c.3184A>G/p.Thr1067Ala polymorphism. Clinical data on all patients were collected retrospectively. The response to AEDs was classified as seizure remission (a minimum of one year of seizure freedom before inclusion) or no remission. Univariate and multivariate logistic regression was used to determine the association of genotypes with binary outcomes.

Results: 114 patients (52.8%) had achieved remission, while 102 (47.2%) had failed to do so. Carriers of at least one polymorphic SCN1A c.3184A>G/p.Thr1067Ala G allele tended to have a lower epilepsy risk (OR=0.38, 95% CI=0.18-0.79, P=0.010) and were significantly more likely to achieve remission (OR=2.00, 95% CI=1.16-3.46, P=0.013). Girls were less likely to achieve remission (P=0.055). Patients in remission tended to be older at first seizure in comparison to the group failing to achieve remission (OR=1.06, 95% CI=0.99-1.14, P=0.099), but this association did not reach statistical significance.

Conclusion: The polymorphic SCN1A c.3184A>G/p.Thr1067Ala G allele was associated with a lower risk of epilepsy and a higher remission rate in Slovenian children and adolescents with epilepsy.