Genetic polymorphisms of CYP3A5, CHRM2, and ZNF498 and their association with epilepsy susceptibility: a pharmacogenetic and case-control study

Laith N Al-Eitan; Islam M Al-Dalalah; Mohamed M Mustafa; Mansour A Alghamdi; Afrah K Elshammari; Wael H Khreisat; Mohammed N Al-Quasmi; Hanan A Aljamal

doi:10.2147/PGPM.S212433

Genetic polymorphisms of CYP3A5, CHRM2, and ZNF498 and their association with epilepsy susceptibility: a pharmacogenetic and case-control study

Pharmgenomics Pers Med. 2019 Sep 4:12:225-233. doi: 10.2147/PGPM.S212433. eCollection 2019.

Authors

Laith N Al-Eitan^{1

2}, Islam M Al-Dalalah¹, Mohamed M Mustafa³, Mansour A Alghamdi⁴, Afrah K Elshammari⁵, Wael H Khreisat⁵, Mohammed N Al-Quasmi⁶, Hanan A Aljamal¹

Affiliations

¹ Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan.
² Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan.
³ Department of Neuroscience, Jordan University of Science and Technology, Irbid, Jordan.
⁴ Anatomy Department, College of Medicine, King Khalid University, Abha, Saudi Arabia.
⁵ Department of Pediatric Neurology, Queen Rania Hospital for Children, King Hussein Medical Center, Royal Medical Services, Amman, Jordan.
⁶ Department of Medical Laboratory, King Abdullah University Hospital, Irbid, Jordan.

Abstract

Background: A total of 50 million persons were diagnosed worldwide with epilepsy. One-third of them are experiencing debilitating seizures despite optimum anti-epileptic drugs (AEDs) treatment. Several studies have suggested that CYP3A5, CHRM2, and ZNF498 influence the pharmacokinetics of AEDs. Therefore, the severity of the disease as well as the degree of response to the AEDs could be affected by the genetic polymorphisms within these genes.

Objectives: In this study, we assessed the effect of certain single nucleotide polymorphisms (SNPs) within CYP3A5, CHRM2, and ZNF498 genes on the susceptibility to develop epilepsy and the responsiveness to AEDs treatment.

Methods: A case-control and pharmacogenetic study was conducted on samples of 299 healthy individuals in addition to 296 epileptic patients. Genotypic, allelic, and clinical data association were performed for the selected polymorphisms within the (rs324649, rs420817, rs15524, and rs1859690) in the Jordanian population.

Results: The analysis revealed no significant association of the investigated SNPs with epilepsy in general, partial and generalized epilepsy as well as drug responsiveness. CYP3A5 and ZNF498 were associated with family history (P=0.003 and P=0.002, respectively) and the classification of epilepsy for the ZNF498 variant (P=0.009). On the other hand, CHRM2 was not linked to either disease severity or treatment responsiveness.

Conclusion: Our results failed to confirm the association of CYP3A5, ZNF498, and CHRM2 variants with either disease development or treatment response. Clinical pharmacogenetic studies may contribute to treatment personalization, appropriate drug dose selection, minimizing drug adverse reactions, increasing drug efficacy, and reducing the costive burdens.

Keywords: anti-epileptic drugs; cytochrome P-450 CYP3A; epilepsy; humans; pharmacogenetics; seizures.