AUTHOR=Wang Shitao , Cai Xuemei , Liu Shiyong , Zhou Qixin , Wang Ting , Du Sunbing , Wang Dan , Yang Fei , Wu Qian , Han Yanbing 

TITLE=A novel BCL11A polymorphism influences gene expression, therapeutic response and epilepsy risk: A multicenter study

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=15

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.1010101

DOI=10.3389/fnmol.2022.1010101

ISSN=1662-5099

ABSTRACT=<sec><title>Background</title><p>Genetic factors have been found to be associated with the efficacy and adverse reactions of antiseizure medications. <italic>BCL11A</italic> is an important regulator of the development of neuronal networks. However, the role of <italic>BCL11A</italic> in epilepsy remains unclear. This study aimed to evaluate the genetic association of <italic>BCL11A</italic> with the susceptibility to develop epileptic seizures and therapeutic response of patients with epilepsy in Han Chinese.</p></sec><sec><title>Methods</title><p>We matched 450 epilepsy cases with 550 healthy controls and 131 drug-resistant epilepsy patients with 319 drug-responsive epilepsy patients from two different centers. Genetic association analysis, genetic interaction analysis, expression quantitative trait loci analysis and protein–protein interaction analysis were conducted.</p></sec><sec><title>Results</title><p>Our results showed that rs2556375 not only increases susceptibility to develop epileptic seizures (OR = 2.700, 95% = 1.366–5.338, <italic>p</italic> = 0.004 and OR = 2.984, 95% = 1.401–6.356, <italic>p</italic> = 0.005, respectively), but also increases the risk of drug resistance(OR = 21.336, 95%CI =2.489–183.402, <italic>p</italic> = 0.005). The interaction between rs2556375 and rs12477097 results in increased risk for pharma coresistant. In addition, rs2556375 regulated <italic>BCL11A</italic> expression in human brain tissues (<italic>p</italic> = 0.0096 and <italic>p</italic> = 0.033, respectively). Furthermore, the protein encoded by <italic>BCL11A</italic> interacted with targets of approved antiepileptic drugs.</p></sec><sec><title>Conclusion</title><p><italic>BCL11A</italic> may be a potential therapeutic target for epilepsy. Rs2556375 may increase the risks of epilepsy and drug resistance by regulating <italic>BCL11A</italic> expression in human brain tissues. Moreover, the interaction between rs2556375 and rs12477097 results in increased risk for drug resistance.</p></sec>