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Background:   SCN1A  and  SCN2A  genes have been reported to be associated with the efficacy of single and combined antiepileptic therapy, but the results remain contradictory. Previous meta-analyses on this topic mainly focused on the  SCN1A  rs3812718 polymorphism. However, meta-analyses focused on  SCN1A  rs2298771,  SCN1A  rs10188577,  SCN2A  rs17183814, or  SCN2A  rs2304016 polymorphisms are scarce or non-existent.   Objective:  We aimed to conduct a meta-analysis to determine the effects of  SCN1A  rs2298771,  SCN1A  rs10188577,  SCN2A  rs17183814, and  SCN2A  rs2304016 polymorphisms on resistance to antiepileptic drugs (AEDs).   Methods:  We searched the PubMed, Embase, Cochrane Library, WANFANG, and CNKI databases up to June 2020 to collect studies on the association of  SCN1A  and  SCN2A  polymorphisms with reactivity to AEDs. We calculated the pooled odds ratios (ORs) under the allelic, homozygous, heterozygous, dominant, and recessive genetic models to identify the association between the four single-nucleotide polymorphisms (SNPs) and resistance to AEDs.   Results:  Our meta-analysis included 19 eligible studies. The results showed that the  SCN1A  rs2298771 polymorphism was related to AED resistance in the allelic, homozygous, and recessive genetic models (G vs. A: OR = 1.20, 95% CI: 1.012–1.424; GG vs. AA: OR = 1.567, 95% CI: 1.147–2.142; GG vs. AA + AG: OR = 1.408, 95% CI: 1.053–1.882). The homozygous model remained significant after Bonferroni correction ( P  < 0.0125). Further subgroup analyses demonstrated the significance of the correlation in the dominant model in Caucasians (South Asians) after Bonferroni correction (GG + GA vs. AA: OR = 1.620, 95% CI: 1.165–2.252). However, no association between  SCN1A  rs2298771 polymorphism and resistance to AEDs was found in Asians or Caucasians (non-South Asians). For  SCN1A  rs10188577,  SCN2A  rs17183814, and  SCN2A  rs2304016 polymorphisms, the correlations with responsiveness to AEDs were not significant in the overall population nor in any subgroup after conducting the Bonferroni correction. The results for  SCN1A  rs2298771,  SCN1A  rs10188577, and  SCN2A  rs2304016 polymorphisms were stable and reliable according to sensitivity analysis and Begg and Egger tests. However, the results for  SCN2A  rs17183814 polymorphism have to be treated cautiously owing to the significant publication bias revealed by Begg and Egger tests.   Conclusions:  The present meta-analysis indicated that  SCN1A  rs2298771 polymorphism significantly affects resistance to AEDs in the overall population and Caucasians (South Asians). There were no significant correlations between  SCN1A  rs10188577,  SCN2A  rs17183814, and  SCN2A  rs2304016 polymorphisms and resistance to AEDs.

frontiers in neurology

Association Between SCN1A rs2298771, SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 Polymorphisms and Responsiveness to Antiepileptic Drugs: A Meta-Analysis