Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Neurology, Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Epilepsia Open. 2023 Jun;8(2):509-516. doi: 10.1002/epi4.12727. Epub 2023 Mar 22.
We aimed to explore the underlying pathomechanisms of the comorbidity between three common systemic autoimmune disorders (SADs) [i.e., insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA)] and temporal lobe epilepsy (TLE), using bioinformatics tools. We hypothesized that there are shared genetic variations among these four conditions.
Different databases (DisGeNET, Harmonizome, and Enrichr) were searched to find TLE-associated genes with variants; their single nucleotide polymorphisms (SNPs) were gathered from the literature. We also did a separate literature search using PubMed with the following keywords for original articles: "TLE" or "Temporal lobe epilepsy" AND "genetic variation," "single nucleotide polymorphism," "SNP," or "genetic polymorphism." In the next step, the SNPs associated with TLE were searched in the LitVar database to find the shared gene variations with RA, SLE, and IDDM.
Ninety unique SNPs were identified to be associated with TLE. LitVar search identified two SNPs that were shared between TLE and all three SADs (i.e., IDDM, SLE, and RA). The first SNP was rs16944 on the Interleukin-1β (IL-1β) gene. The second genetic variation was ε4 variation of apolipoprotein E (APOE) gene.
The shared genetic variations (i.e., rs16944 on the IL-1β gene and ε4 variation of the APOE gene) may explain the underlying pathomechanisms of the comorbidity between three common SADs (i.e., IDDM, SLE, and RA) and TLE. Exploring such shared genetic variations may help find targeted therapies for patients with TLE, especially those with drug-resistant seizures who also have comorbid SADs.
我们旨在使用生物信息学工具探索三种常见的系统性自身免疫性疾病（SADs）[即胰岛素依赖型糖尿病（IDDM）、系统性红斑狼疮（SLE）和类风湿关节炎（RA）]与颞叶癫痫（TLE）之间共病的潜在病理机制。我们假设这四种疾病存在共同的遗传变异。
使用不同的数据库（DisGeNET、Harmonizome 和 Enrichr）搜索与 TLE 相关的具有变异的基因；从文献中收集它们的单核苷酸多态性（SNP）。我们还使用 PubMed 进行了单独的文献搜索，使用的关键词为原始文章：“TLE”或“颞叶癫痫”和“遗传变异”、“单核苷酸多态性”、“SNP”或“遗传多态性”。在下一步中，在 LitVar 数据库中搜索与 TLE 相关的 SNPs，以找到与 RA、SLE 和 IDDM 共有的基因变异。
确定了 90 个与 TLE 相关的独特 SNP。LitVar 搜索发现了两个与 TLE 和所有三种 SAD（即 IDDM、SLE 和 RA）都相关的 SNP。第一个 SNP 是白细胞介素 1β（IL-1β）基因上的 rs16944。第二个遗传变异是载脂蛋白 E（APOE）基因的 ε4 变异。
共同的遗传变异（即 IL-1β 基因上的 rs16944 和 APOE 基因的 ε4 变异）可能解释了三种常见 SAD（即 IDDM、SLE 和 RA）与 TLE 之间共病的潜在病理机制。探索这种共同的遗传变异可能有助于为 TLE 患者找到靶向治疗方法，特别是那些患有药物抵抗性癫痫且同时患有 SAD 的患者。
