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J. Pers. Med. 2018, 8(4), 37; https://doi.org/10.3390/jpm8040037

The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy

1
Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan
2
Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan
3
Queen Rania hospital for children, King Hussein Medical Centre, Royal medical services (RMS), Amman 11118, Jordan
*
Author to whom correspondence should be addressed.
Received: 13 October 2018 / Revised: 27 October 2018 / Accepted: 8 November 2018 / Published: 14 November 2018
(This article belongs to the Special Issue Personalized Medicine Based on Drug Transporter Genetic Heterogeneity)
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Abstract

This study aims to investigate the effects of the three potassium channel genes KCNA1, KCNA2, and KCNV2 on increased susceptibility to epilepsy as well as on responsiveness to antiepileptic drugs (AEDs). The pharmacogenetic and case-control cohort (n = 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 (KCNA1, KCNA2, and KCNV2). Only one SNP in KCNA2, rs3887820, showed significant association with increased risk of susceptibility to generalized myoclonic seizure (p-value < 0.001). Notably, the rs112561866 polymorphism of the KCNA1 gene was non-polymorphic, but no significant association was found between the KCNA1 (rs2227910, rs112561866, and rs7974459) and KCNV2 (rs7029012, rs10967705, and rs10967728) polymorphisms and disease susceptibility or drug responsiveness among Jordanian patients. This study suggests that a significant association exists between the KCNA2 SNP rs3887820 and increased susceptibility to generalized myoclonic seizure. However, the present findings indicate that the KCNA1 and KCNV2 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. View Full-Text
Keywords: epilepsy; potassium channels; pharmacogenetics; antiepileptic drug epilepsy; potassium channels; pharmacogenetics; antiepileptic drug
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AL-Eitan, L.N.; Al-Dalalah, I.M.; Elshammari, A.K.; Khreisat, W.H.; Almasri, A.Y. The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy. J. Pers. Med. 2018, 8, 37.

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