Al-Eitan Laith N, Al-Dalalah Islam M, Elshammari Afrah K, Khreisat Wael H, Almasri Ayah Y
Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan.
Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan.
J Pers Med. 2018 Nov 14;8(4):37. doi: 10.3390/jpm8040037.
This study aims to investigate the effects of the three potassium channel genes , , and on increased susceptibility to epilepsy as well as on responsiveness to antiepileptic drugs (AEDs). The pharmacogenetic and case-control cohort ( = 595) consisted of 296 epileptic patients and 299 healthy individuals. Epileptic patients were recruited from the Pediatric Neurology clinic at the Queen Rania Al Abdullah Hospital (QRAH) in Amman, Jordan. A custom platform array search for genetic association in Jordanian-Arab epileptic patients was undertaken. The MassARRAY system (iPLEX GOLD) was used to genotype seven single nucleotide polymorphisms (SNPs) within three candidate genes (, , and ). Only one SNP in , rs3887820, showed significant association with increased risk of susceptibility to generalized myoclonic seizure (-value < 0.001). Notably, the rs112561866 polymorphism of the gene was non-polymorphic, but no significant association was found between the (rs2227910, rs112561866, and rs7974459) and (rs7029012, rs10967705, and rs10967728) polymorphisms and disease susceptibility or drug responsiveness among Jordanian patients. This study suggests that a significant association exists between the SNP rs3887820 and increased susceptibility to generalized myoclonic seizure. However, the present findings indicate that the and SNPs do not influence disease susceptibility and drug responsiveness in epileptic patients. Pharmacogenetic and case-control studies involving a multicenter and multiethnic approach are needed to confirm our results. To improve the efficacy and safety of epilepsy treatment, further studies are required to identify other genetic factors that contribute to susceptibility and treatment outcome.
本研究旨在调查三种钾通道基因（ 、 和 ）对癫痫易感性增加以及对抗癫痫药物（AEDs）反应性的影响。药物遗传学和病例对照队列（ = 595）由296例癫痫患者和299名健康个体组成。癫痫患者来自约旦安曼拉尼亚王后阿卜杜拉医院（QRAH）的儿科神经科诊所。对约旦 - 阿拉伯癫痫患者进行了定制平台阵列的基因关联搜索。使用MassARRAY系统（iPLEX GOLD）对三个候选基因（ 、 和 ）内的七个单核苷酸多态性（SNP）进行基因分型。只有 基因中的一个SNP，rs3887820，显示与全身性肌阵挛发作易感性增加的风险有显著关联（ - 值 < 0.001）。值得注意的是， 基因的rs112561866多态性是非多态性的，但在约旦患者中， （rs2227910、rs112561866和rs7974459）和 （rs7029012、rs10967705和rs10967728）多态性与疾病易感性或药物反应性之间未发现显著关联。本研究表明， 基因的SNP rs3887820与全身性肌阵挛发作易感性增加之间存在显著关联。然而，目前的研究结果表明， 和 基因的SNP不影响癫痫患者的疾病易感性和药物反应性。需要采用多中心和多民族方法进行药物遗传学和病例对照研究以证实我们的结果。为了提高癫痫治疗的疗效和安全性，需要进一步研究以确定其他影响易感性和治疗结果的遗传因素。
