Qu Jian, Lu Shao-Hua, Lu Zhi-Li, Xu Ping, Xiang Da-Xiong, Qu Qiang
Department of Pharmacy, the Second Xiangya Hospital, Central South University, Institute of Clinical Pharmacy Department of Neurosurgery, the Third Xiangya Hospital Department of Pathology, the Affiliated Cancer Hospital of Xiangya School of Medicine Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, P. R. China.
Medicine (Baltimore). 2017 Jun;96(26):e7321. doi: 10.1097/MD.0000000000007321.
Potassium channels are the targets of antiepileptic drugs (AEDs), which play important roles in the etiology of epilepsy. KCNA1 and KCNA2 encode mammalian Kv1.1 and Kv1.2 channels, which are essential roles in the initiation and shaping of action potentials. KCNV2 encodes Kv8.2, which is a regional overlap with Kv2 subunits as functional heterotetramers. In our study, we aim to investigate whether variants of KCNA1, KCNA2, and KCNV2 genes influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of AEDs. Seven hundred sixty-seven subjects (284 healthy controls, 279 drug-responsive, and 204 drug-resistant GGE patients) were enrolled in our study. Eight variants of KCNA1, KCNA2, and KCNV2 were assessed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. Results showed that there were no statistically significant correlations between the 8 variants of KCNA1, KCNA2, and KCNV2 and the risk/drug resistance of GGEs. In conclusion, our study suggests that KCNA1, KCNA2, and KCNV2 variants may not be involved in the risk/drug resistance of GGEs. Further multicenter, multiethnic, and large sample size pharmacogenetic and case-control studies are warranted to confirm our negative results.
钾通道是抗癫痫药物（AEDs）的作用靶点，在癫痫病因学中发挥重要作用。KCNA1和KCNA2分别编码哺乳动物的Kv1.1和Kv1.2通道，它们在动作电位的起始和形成过程中起着至关重要的作用。KCNV2编码Kv8.2，其作为功能性异源四聚体与Kv2亚基存在区域重叠。在我们的研究中，我们旨在探究KCNA1、KCNA2和KCNV2基因的变异是否会影响遗传性全身性癫痫（GGEs）的易感性以及AEDs的疗效。我们的研究纳入了767名受试者（284名健康对照者、279名药物反应性GGE患者和204名药物抵抗性GGE患者）。通过基质辅助激光解吸/电离飞行时间质谱法评估了KCNA1、KCNA2和KCNV2的8个变异。结果显示，KCNA1、KCNA2和KCNV2的8个变异与GGEs的风险/药物抵抗之间不存在统计学上的显著相关性。总之，我们的研究表明，KCNA1、KCNA2和KCNV2变异可能不参与GGEs的风险/药物抵抗。有必要进行进一步的多中心、多民族和大样本量的药物遗传学及病例对照研究来证实我们的阴性结果。
