Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India.
Council of Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology (IGIB) Mall Road Delhi 110 007 India; Division of Pneumonology-Immunology Department of Paediatrics Charité University Medical Centre Berlin Germany.
Brain Behav. 2016 Jun 14;6(7):e00490. doi: 10.1002/brb3.490. eCollection 2016 Jul.
"Common epilepsies", merely explored for genetics are the most frequent, nonfamilial, sporadic cases in hospitals. Because of their much debated molecular pathology, there is a need to focus on other neuronal pathways including the existing ion channels.
For this study, a total of 214 epilepsy cases of North Indian ethnicity comprising 59.81% generalized, 40.19% focal seizures, and based on epilepsy types, 17.29% idiopathic, 37.38% cryptogenic, and 45.33% symptomatic were enrolled. Additionally, 170 unrelated healthy individuals were also enrolled. Here, we hypothesize the involvement of epilepsy pathophysiology genes, that is, synaptic vesicle cycle, SVC genes (presynapse), ion channels and their functionally related genes (postsynapse). An interactive analysis was initially performed in SVC genes using multifactor dimensionality reduction (MDR). Further, in order to understand the influence of ion channels and their functionally related genes, their interaction analysis with SVC genes was also performed.
A significant interactive two-locus model of STX1A_rs4363087|VAMP2_rs2278637 (presynaptic genes) was observed among SVC variants in all epilepsy cases (P 1000-value = 0.054; CVC = 9/10; OR = 2.86, 95%CI = 1.88-4.35). Further, subgroup analysis revealed stronger interaction for the same model in cryptogenic epilepsy patients only (P 1000-value = 0.012; CVC = 10/10; OR = 4.59, 95%CI = 2.57-8.22). However, interactive analysis of presynaptic and postsynaptic genes did not show any significant association.
Significant synergistic interaction of SVC genes revealed the possible functional relatedness of presynapse with pathophysiology of cryptogenic epilepsy. Further, to establish the clinical utility of the results, replication in a large and similar phenotypic group of patients is warranted.
“常见癫痫”仅在遗传学方面进行了探索，是医院中最常见的非家族性、散发性病例。由于其分子病理学存在很大争议，因此需要关注其他神经元途径，包括现有的离子通道。
在这项研究中，共纳入了 214 名北印度裔癫痫患者，其中 59.81%为全面性发作，40.19%为局灶性发作，根据癫痫类型，17.29%为特发性，37.38%为隐源性，45.33%为症状性。此外，还纳入了 170 名无关的健康个体。在这里，我们假设癫痫病理生理学基因（即突触囊泡循环、SVC 基因（突触前）、离子通道及其功能相关基因（突触后））的参与。最初使用多因素维度缩减（MDR）在 SVC 基因中进行了交互分析。此外，为了了解离子通道及其功能相关基因的影响，还对其与 SVC 基因的相互作用进行了分析。
在所有癫痫病例中，观察到 SVC 变异中 STX1A_rs4363087|VAMP2_rs2278637（突触前基因）的显著两基因相互作用模型（P 1000 值=0.054；CVC=9/10；OR=2.86，95%CI=1.88-4.35）。进一步的亚组分析显示，在隐源性癫痫患者中，同一模型的相互作用更强（P 1000 值=0.012；CVC=10/10；OR=4.59，95%CI=2.57-8.22）。然而，突触前和突触后基因的相互作用分析没有显示出任何显著关联。
SVC 基因的显著协同相互作用揭示了突触前与隐源性癫痫病理生理学的可能功能相关性。此外，为了确立结果的临床实用性，需要在具有相似表型的大患者群体中进行复制。
