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

Abstract

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.

Effect of SCN1Aand SCN2A gene polymorphisms on the efficacy of valproic acid treatment in Chinese children with epilepsy

“…Epilepsy is recognized as an ion channel disorder, and voltage-gated ion channels constitute common targets for the action of antiepileptic drugs (ASMs). Variants within the SCN1A and SCN2A genes have been proposed as potential contributors to antiepileptic drug resistance [ 5 ]. Notably, a missense mutation in the SCN1A exonic region (SCN1A rs2298771) results in the substitution of threonine with alanine through a G to A base change [ 6 ].…”

Association between Genetic Polymorphism of SCN1A, GABRA1 and ABCB1 and Drug Responsiveness in Vietnamese Epileptic Children

“…Therefore, these channels are the target of many first-line AEDs that have been widely used. The rs2298771 G > A (p.Thr1067Ala), rs3812718 (IVS5N+5 C > T) and rs10188577 A > G are common polymorphisms of the SCN1A gene, which were extensively studied in various populations regarding their relationship with drug responses [18][19][20][21][22]. For rs2298771 G > A (p.Thr1067Ala), this is a variant in the coding region of the SCN1A gene.…”

Acute liver failure associated with lamotrigine in children with epilepsy: A report of two cases and thoughts on pharmacogenomics

“…Pharmacogenetic testing for these genes may be useful in assessing individual metabolism of LTG [13] . In addition, certain SNPs of genes encoding voltage-gated sodium channels were suggested to be involved in LTG responsiveness and resistance [14] . Case 1 carried UGT1A4 rs2011425 TT and ABCG2 rs3114020 CC, both of which may lead to a possible increase in serum LTG concentration [15] , [16] , but she also had SLC22A1 rs628031 GG which may decrease the concentration, and UGT2B7 rs7668258 CT, which does not affect the concentration in Han Chinese individuals [17] , [18] .…”