The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy
This study aims to investigate the effects of the three potassium channel genes <i>KCNA1</i>, <i>KCNA2</i>, and <i>KCNV2</i> on increased susceptibility to epilepsy as well as on responsiveness to antiepileptic drugs (AEDs). The pharmacogenetic and case-control co...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-11-01
|
| Series: | Journal of Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4426/8/4/37 |
| _version_ | 1797757885594206208 |
|---|---|
| author | Laith N. AL-Eitan Islam M. Al-Dalalah Afrah K. Elshammari Wael H. Khreisat Ayah Y. Almasri |
| author_facet | Laith N. AL-Eitan Islam M. Al-Dalalah Afrah K. Elshammari Wael H. Khreisat Ayah Y. Almasri |
| author_sort | Laith N. AL-Eitan |
| collection | DOAJ |
| description | This study aims to investigate the effects of the three potassium channel genes <i>KCNA1</i>, <i>KCNA2</i>, and <i>KCNV2</i> on increased susceptibility to epilepsy as well as on responsiveness to antiepileptic drugs (AEDs). The pharmacogenetic and case-control cohort (<i>n</i> = 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 (<i>KCNA1</i>, <i>KCNA2</i>, and <i>KCNV2</i>). Only one SNP in <i>KCNA2</i>, rs3887820, showed significant association with increased risk of susceptibility to generalized myoclonic seizure (<i>p</i>-value < 0.001). Notably, the rs112561866 polymorphism of the <i>KCNA1</i> gene was non-polymorphic, but no significant association was found between the <i>KCNA1</i> (rs2227910, rs112561866, and rs7974459) and <i>KCNV2</i> (rs7029012, rs10967705, and rs10967728) polymorphisms and disease susceptibility or drug responsiveness among Jordanian patients. This study suggests that a significant association exists between the <i>KCNA2</i> SNP rs3887820 and increased susceptibility to generalized myoclonic seizure. However, the present findings indicate that the <i>KCNA1</i> and <i>KCNV2</i> 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. |
| first_indexed | 2024-03-12T18:22:00Z |
| format | Article |
| id | doaj.art-419e7ec1f0d24495aa35cb34c742c7a8 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-12T18:22:00Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-419e7ec1f0d24495aa35cb34c742c7a82023-08-02T08:48:58ZengMDPI AGJournal of Personalized Medicine2075-44262018-11-01843710.3390/jpm8040037jpm8040037The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with EpilepsyLaith N. AL-Eitan0Islam M. Al-Dalalah1Afrah K. Elshammari2Wael H. Khreisat3Ayah Y. Almasri4Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, JordanDepartment of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, JordanQueen Rania hospital for children, King Hussein Medical Centre, Royal medical services (RMS), Amman 11118, JordanQueen Rania hospital for children, King Hussein Medical Centre, Royal medical services (RMS), Amman 11118, JordanDepartment of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, JordanThis study aims to investigate the effects of the three potassium channel genes <i>KCNA1</i>, <i>KCNA2</i>, and <i>KCNV2</i> on increased susceptibility to epilepsy as well as on responsiveness to antiepileptic drugs (AEDs). The pharmacogenetic and case-control cohort (<i>n</i> = 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 (<i>KCNA1</i>, <i>KCNA2</i>, and <i>KCNV2</i>). Only one SNP in <i>KCNA2</i>, rs3887820, showed significant association with increased risk of susceptibility to generalized myoclonic seizure (<i>p</i>-value < 0.001). Notably, the rs112561866 polymorphism of the <i>KCNA1</i> gene was non-polymorphic, but no significant association was found between the <i>KCNA1</i> (rs2227910, rs112561866, and rs7974459) and <i>KCNV2</i> (rs7029012, rs10967705, and rs10967728) polymorphisms and disease susceptibility or drug responsiveness among Jordanian patients. This study suggests that a significant association exists between the <i>KCNA2</i> SNP rs3887820 and increased susceptibility to generalized myoclonic seizure. However, the present findings indicate that the <i>KCNA1</i> and <i>KCNV2</i> 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.https://www.mdpi.com/2075-4426/8/4/37epilepsypotassium channelspharmacogeneticsantiepileptic drug |
| spellingShingle | Laith N. AL-Eitan Islam M. Al-Dalalah Afrah K. Elshammari Wael H. Khreisat Ayah Y. Almasri The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy Journal of Personalized Medicine epilepsy potassium channels pharmacogenetics antiepileptic drug |
| title | The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy |
| title_full | The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy |
| title_fullStr | The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy |
| title_full_unstemmed | The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy |
| title_short | The Impact of Potassium Channel Gene Polymorphisms on Antiepileptic Drug Responsiveness in Arab Patients with Epilepsy |
| title_sort | impact of potassium channel gene polymorphisms on antiepileptic drug responsiveness in arab patients with epilepsy |
| topic | epilepsy potassium channels pharmacogenetics antiepileptic drug |
| url | https://www.mdpi.com/2075-4426/8/4/37 |
| work_keys_str_mv | AT laithnaleitan theimpactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy AT islammaldalalah theimpactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy AT afrahkelshammari theimpactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy AT waelhkhreisat theimpactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy AT ayahyalmasri theimpactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy AT laithnaleitan impactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy AT islammaldalalah impactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy AT afrahkelshammari impactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy AT waelhkhreisat impactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy AT ayahyalmasri impactofpotassiumchannelgenepolymorphismsonantiepilepticdrugresponsivenessinarabpatientswithepilepsy |