AUTHOR=Wang Shitao , Zhou Liang , He Chenglu , Wang Dan , Cai Xuemei , Yu Yanying , Chen Liling , Lu Di , Bian Ligong , Du Sunbing , Wu Qian , Han Yanbing 

TITLE=The Association Between STX1B Polymorphisms and Treatment Response in Patients With Epilepsy

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.701575

DOI=10.3389/fphar.2021.701575

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Epilepsy is a debilitating brain disease with complex inheritance and frequent treatment resistance. However, the role of <italic>STX1B</italic> single nucleotide polymorphisms (SNPs) in epilepsy treatment remains unknown.</p><p><bold>Objective:</bold> This study aimed to explore the genetic association of <italic>STX1B</italic> SNPs with treatment response in patients with epilepsy in a Han Chinese population.</p><p><bold>Methods:</bold> We first examined the associations between <italic>STX1B</italic> SNPs and epilepsy in 1000 Han Chinese and the associations between <italic>STX1B</italic> SNPs and drug-resistant epilepsy in 450 subjects. Expression quantitative trait loci analysis was then conducted using 16 drug-resistant epileptic brain tissue samples and results from the BrainCloud database (<ext-link ext-link-type="uri" xlink:href="http://eqtl.brainseq.org" xmlns:xlink="http://www.w3.org/1999/xlink">http://eqtl.brainseq.org</ext-link>).</p><p><bold>Results:</bold> The allelic frequencies of rs140820592 were different between the epilepsy and control groups (<italic>p</italic> = 0.002) after Bonferroni correction. The rs140820592 was associated with significantly lower epilepsy risk among 1,000 subjects in the dominant model after adjusting for gender and age and Bonferroni correction (OR = 0.542, 95%CI = 0.358–0.819, <italic>p</italic> = 0.004). The rs140820592 also conferred significantly lower risk of drug-resistant epilepsy among 450 subjects using the same dominant model after adjusting for gender and age and Bonferroni correction (OR = 0.260, 95%CI = 0.103–0.653, <italic>p</italic> = 0.004). Expression quantitative trait loci analysis revealed that rs140820592 was associated with <italic>STX1B</italic> expression level in drug-resistant epileptic brain tissues (<italic>p</italic> = 0.012), and this result was further verified in the BrainCloud database (<ext-link ext-link-type="uri" xlink:href="http://eqtl.brainseq.org" xmlns:xlink="http://www.w3.org/1999/xlink">http://eqtl.brainseq.org</ext-link>) (<italic>p</italic> = 2.3214 × 10<sup>–5</sup>).</p><p><bold>Conclusion:</bold> The <italic>STX1B</italic> rs140820592 may influence the risks of epilepsy and drug-resistant epilepsy by regulating <italic>STX1B</italic> expression in brain tissues.</p>