Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds, Post Graduate Program in Health Science, São Francisco University (USF), Avenida São Francisco de Assis, 218, Jardim São José, Bragança Paulista, São Paulo, 12916-900, Brazil.
Laboratory of Human and Medical Genetics, Post Graduate Program in Health Science, USF, Avenida São Francisco de Assis, 218, Jardim São José, Bragança Paulista, São Paulo, 12916-900, Brazil.
Cell Mol Neurobiol. 2022 Aug;42(6):1645-1658. doi: 10.1007/s10571-021-01058-7. Epub 2021 Mar 5.
Single-nucleotide variant (SNV) is a single base mutation at a specific location in the genome and may play an import role in epilepsy pathophysiology. The aim of this study was to review case-control studies that have investigated the relationship between SNVs within microRNAs (miRs) sequences or in their target genes and epilepsy susceptibility from January 1, 2010 to October 31, 2020. Nine case-control studies were included in the present review. The mainly observed SNVs associated with drug-resistant epilepsy (DRE) risk were SNVs n.60G > C (rs2910164) and n.-411A > G (rs57095329), both located at miR-146a mature sequence and promoter region, respectively. In addition, the CC haplotype (rs987195-rs969885) and the AA genotype at rs4817027 in the MIR155HG/miR-155 tagSNV were also genetic susceptibility markers for early-onset epilepsy. MiR-146a has been observed as upregulated in human astrocytes in epileptogenesis and it regulates inflammatory process through NF-κB signaling by targeting tumor necrosis factor-associated factor 6 (TRAF6) gene. The SNVs rs2910164 and rs57095329 may modify the expression level of mature miR-146a and the risk for epilepsy and SNVs located at rs987195-rs969885 haplotype and at rs4817027 in the MIR155HG/miR-155 tagSNV could interfere in the miR-155 expression modulating inflammatory pathway genes involved in the development of early-onset epilepsy. In addition, SNVs rs662702, rs3208684, and rs35163679 at 3'untranslated region impairs the ability of miR-328, let-7b, and miR-200c binding affinity with paired box protein PAX-6 (PAX6), BCL2 like 1 (BCL2L1), and DNA methyltransferase 3 alpha (DNMT3A) target genes. The SNV rs57095329 might be correlated with DRE when a larger number of patients are evaluated. Thus, we concluded that the main drawback of most of studies is the small number of individuals enrolled, which lacks sample power.
单核苷酸变异 (SNV) 是基因组特定位置的单个碱基突变，可能在癫痫发病机制中发挥重要作用。本研究旨在回顾 2010 年 1 月 1 日至 2020 年 10 月 31 日期间，研究微 RNA (miRs) 序列或其靶基因中 SNV 与癫痫易感性之间关系的病例对照研究。本综述纳入了 9 项病例对照研究。与耐药性癫痫 (DRE) 风险相关的主要观察到的 SNV 是位于 miR-146a 成熟序列和启动子区域的 SNV n.60G>C(rs2910164)和 n.-411A>G(rs57095329)。此外，CC 单倍型(rs987195-rs969885)和 MIR155HG/miR-155 标记 SNV 处 rs4817027 的 AA 基因型也是早发性癫痫的遗传易感性标志物。在癫痫发生过程中，miR-146a 在人类星形胶质细胞中被观察到上调，它通过靶向肿瘤坏死因子相关因子 6 (TRAF6) 基因调节 NF-κB 信号通路来调节炎症过程。SNV rs2910164 和 rs57095329 可能改变成熟 miR-146a 的表达水平和癫痫风险，位于 rs987195-rs969885 单倍型和 MIR155HG/miR-155 标记 SNV 处 rs4817027 的 SNV 可能干扰调节炎症途径基因的 miR-155 表达，这些基因参与早发性癫痫的发生。此外，3'非翻译区的 SNV rs662702、rs3208684 和 rs35163679 会损害 miR-328、let-7b 和 miR-200c 与配对盒蛋白 PAX-6 (PAX6)、BCL2 样 1 (BCL2L1) 和 DNA 甲基转移酶 3α (DNMT3A) 靶基因的结合亲和力。当评估更多患者时，SNV rs57095329 可能与 DRE 相关。因此，我们得出结论，大多数研究的主要缺点是纳入的个体数量较少，缺乏样本量。
