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

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