Al-Eitan Laith N, Al-Dalalah Islam M, Aljamal Hanan A
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.
Saudi Pharm J. 2019 Jul;27(5):731-737. doi: 10.1016/j.jsps.2019.04.009. Epub 2019 Apr 24.
Pharmacotherapy of epilepsy including antiepileptic drugs (AEDs) is one of the main treatment approaches. As a biological target, sodium channels (Nav channels) and glutamate receptor genes are playing a major role in the etiology and treatment of epilepsy.
This study aims to investigate the genetic associations of certain genetic polymorphisms with increased risk of epilepsy susceptibility and variability in response to AEDs treatment in a Jordanian Arab population.
A pharmacogenetics and case-control study on 296 unrelated epileptic Jordanian patients recruited from the pediatric neurology clinic at the Queen Rania Al-Abdullah Hospital (QRAH) in Amman, Jordan and 299 healthy individuals was conducted. Children up to 15 years old which receiving AEDs for at least three months were scanned for genetic association of 7 single nucleotide polymorphisms (SNPs) within three candidate genes (, and ) with epilepsy susceptibility.
SCN2A rs2304016 ( = 0.04) and GRM4 rs2499697 ( = 0.031) were statistically significant with generalized epilepsy. Haplotype of CAACG GRM4 was genetically associated with epilepsy and partial epilepsy ( = 0.036; = 0.024, respectively). This study also found that TGTAA genetic haplotype formed within gene was associated with generalized epilepsy susceptibility ( = 0.006). While, no significant linkage of SCN3B rs3851100 to either disease susceptibility or drug responsiveness was found.
This study identified no significant associations of allelic or genotypic SNPs with the susceptibility of epilepsy and medication response with an exception of rs2304016 and rs2499697 SNPs that were associated with the generalized type of epilepsy among Jordanian population. Further studies are required in different populations to confirm our results and identify genetic factors that involved in susceptibility and treatment response.
癫痫的药物治疗，包括抗癫痫药物（AEDs），是主要的治疗方法之一。作为生物学靶点，钠通道（Nav通道）和谷氨酸受体基因在癫痫的病因和治疗中起着重要作用。
本研究旨在调查约旦阿拉伯人群中某些基因多态性与癫痫易感性增加及AEDs治疗反应变异性之间的遗传关联。
对从约旦安曼王后拉尼娅·阿卜杜拉医院（QRAH）儿科神经科诊所招募的296名无亲缘关系的约旦癫痫患者和299名健康个体进行了药物遗传学和病例对照研究。对15岁以下接受AEDs治疗至少三个月的儿童进行扫描，以检测三个候选基因（、和）内7个单核苷酸多态性（SNP）与癫痫易感性的遗传关联。
SCN2A rs2304016（=0.04）和GRM4 rs2499697（=0.031）与全身性癫痫具有统计学意义。GRM4的CAACG单倍型与癫痫和部分性癫痫存在遗传关联（分别为=0.036；=0.024）。本研究还发现，基因内形成的TGTAA遗传单倍型与全身性癫痫易感性相关（=0.006）。而未发现SCN3B rs3851100与疾病易感性或药物反应性有显著关联。
本研究发现，除了rs2304016和rs2499697这两个与约旦人群全身性癫痫相关的SNP外，等位基因或基因型SNP与癫痫易感性和药物反应性之间无显著关联。需要在不同人群中进行进一步研究，以证实我们的结果，并确定参与易感性和治疗反应的遗传因素。
