Association between two SCN1A polymorphisms and resistance to sodium channel blocking AEDs: a meta-analysis

Sodium channel blocking antiepileptic drugs (SCB-AEDs) are common effective medications available for epilepsy. However, not all patients respond to this regimen and drug resistance is frequently encountered. Rs2298771(c.3184A > G/p.Thr1067Ala) and rs3812718(IVS5N +5G > A) polymorphisms are two of the most common polymorphisms in the SCN1A gene, which is closely related to resistance to SCB-AEDs. Therefore, we have conducted a meta-analysis to investigate the contribution of the two polymorphisms to resistance of SCB-AEDs. The PubMed, Embase, MEDLINE, and Cochrane Library databases were searched up to September 2017, for studies on the association of SCN1A polymorphisms with resistance to SCB-AEDs. A fixed-effects or random-effects model was used to calculate the pooled odds ratios based on the results from the heterogeneity tests. A total of eight studies were eligible for the pooled analysis, of which eight studies included SCN1A rs3812718 polymorphism and four studies included SCN1A rs2298771 polymorphism. The results showed that SCN1A rs2298771 polymorphism was significantly associated with resistance to SCB-AEDs. (A vs. G: OR = 0.76, 95% CI 0.61–0.95, P = 0.02; AA vs. AG + GG: OR = 0.71, 95% CI 0.54–0.94, P = 0.022). However, no association was observed between SCN1A rs3812718 polymorphism and resistance to SCB-AEDs. Our results indicate that the A-allele of SCN1A rs2298771 polymorphism, especially AA genotype, may play an important role in responsiveness to SCB-AEDs, while SCN1A rs3812718 polymorphism is not associated with SCB-AEDs.