AUTHOR=Li Mengmeng , Zhong Rui , Lu Yingxue , Zhao Qian , Li Guangjian , Lin Weihong 

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

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.591828

DOI=10.3389/fneur.2020.591828

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold><italic>SCN1A</italic> and <italic>SCN2A</italic> 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 <italic>SCN1A</italic> rs3812718 polymorphism. However, meta-analyses focused on <italic>SCN1A</italic> rs2298771, <italic>SCN1A</italic> rs10188577, <italic>SCN2A</italic> rs17183814, or <italic>SCN2A</italic> rs2304016 polymorphisms are scarce or non-existent.</p><p><bold>Objective:</bold> We aimed to conduct a meta-analysis to determine the effects of <italic>SCN1A</italic> rs2298771, <italic>SCN1A</italic> rs10188577, <italic>SCN2A</italic> rs17183814, and <italic>SCN2A</italic> rs2304016 polymorphisms on resistance to antiepileptic drugs (AEDs).</p><p><bold>Methods:</bold> We searched the PubMed, Embase, Cochrane Library, WANFANG, and CNKI databases up to June 2020 to collect studies on the association of <italic>SCN1A</italic> and <italic>SCN2A</italic> 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.</p><p><bold>Results:</bold> Our meta-analysis included 19 eligible studies. The results showed that the <italic>SCN1A</italic> 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 (<italic>P</italic> &lt; 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 <italic>SCN1A</italic> rs2298771 polymorphism and resistance to AEDs was found in Asians or Caucasians (non-South Asians). For <italic>SCN1A</italic> rs10188577, <italic>SCN2A</italic> rs17183814, and <italic>SCN2A</italic> 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 <italic>SCN1A</italic> rs2298771, <italic>SCN1A</italic> rs10188577, and <italic>SCN2A</italic> rs2304016 polymorphisms were stable and reliable according to sensitivity analysis and Begg and Egger tests. However, the results for <italic>SCN2A</italic> rs17183814 polymorphism have to be treated cautiously owing to the significant publication bias revealed by Begg and Egger tests.</p><p><bold>Conclusions:</bold> The present meta-analysis indicated that <italic>SCN1A</italic> rs2298771 polymorphism significantly affects resistance to AEDs in the overall population and Caucasians (South Asians). There were no significant correlations between <italic>SCN1A</italic> rs10188577, <italic>SCN2A</italic> rs17183814, and <italic>SCN2A</italic> rs2304016 polymorphisms and resistance to AEDs.</p>