<p>Genetic Association of Epilepsy and Anti-Epileptic Drugs Treatment in Jordanian Patients</p>

Abstract

The aim of this study was to investigate the possible effects of single-nucleotide polymorphisms (SNPs) within SLC1A1, SLC6A1, FAM131B, GPLD1, F2, GABRG2, GABRA1, and CACNG5 genes on response to anti-epileptic drugs (AEDs) and the genetic predisposition of epilepsy in Jordanian patients. Patients and Methods: A total of 299 healthy individuals and 296 pediatric patients from the Jordanian population were recruited. Blood samples are collected, and genotyping was performed using a custom platform array analysis. Results: The SLC1A1 rs10815018 and FAM131B rs4236482 polymorphisms found to be associated with epilepsy susceptibility. Moreover, SLC1A1 rs10815018 and GPLD1 rs1126617 polymorphisms were associated with generalized epilepsy (GE), while FAM131B rs4236482 is associated with the focal phenotype. Regarding the therapeutic response, the genetic polymorphisms of FAM131B rs4236482, GABRA1 rs2279020, and CACNG5 rs740805 are conferred poor response (resistance) to AEDs. There was no linkage of GLPD1 haplotypes to epilepsy, its subtypes, and treatment responsiveness. Conclusion: Our findings suggested that SLC1A1, FAM131B, and GPLD1 polymorphisms increasing the risk of generating epilepsy, while FAM131B, GABRA1, and CACNG5 variants may play a role in predicting drug response in patients with epilepsy (PWE).

No association of GABRA1 rs2279020 and GABRA6 rs3219151 polymorphisms with risk of epilepsy and antiepileptic drug responsiveness in Asian and Arabic populations: Evidence from a meta-analysis with trial sequential analysis

“…A significant association of the rs2279020 with epilepsy risk was reported by some research groups (16, 26, 32), whereas no significant association was reported by other research groups (13,17,23,25). The controversial results were also observed in comparison to the rs2279020 with AED resistance (16,17,24,25). For example, some authors reported that the rs2279020 was a risk factor for affecting treatment efficacy (16,17).…”

“…Previously, an SNP located in intron 10 of GABRA1 (rs2279020) was reported to be potentially functional, with the A→ G shift changing the shape of the protein that led to alternative splicing (32). A significant association of the rs2279020 with epilepsy risk was reported by some research groups (16, 26, 32), whereas no significant association was reported by other research groups (13,17,23,25). The controversial results were also observed in comparison to the rs2279020 with AED resistance (16,17,24,25).…”

“…The controversial results were also observed in comparison to the rs2279020 with AED resistance (16,17,24,25). For example, some authors reported that the rs2279020 was a risk factor for affecting treatment efficacy (16,17). However, some authors reported that the rs2279020 was not associated with AED resistance (24, 25).…”

“…Single nucleotide polymorphisms (SNP) in any of the subunits may alter the expression of GABA, and ultimately influence epilepsy seizures and responsiveness to AEDs ( 13 – 15 ). For example, Kumari et al reported that the rs2279020 G allele in GABRA1 conferred a high risk of epilepsy and multiple drug resistance ( 16 ), whereas Al-Eitan et al reported that the rs2279020 polymorphism did not show any linkage with the occurrence of epilepsy and treatment responsiveness ( 17 ). Given the conflicting results, a meta-analysis is of great importance to be performed to obtain the real effect of the rs2279020 on epilepsy risk.…”

Pharmacogenetics in Primary Headache Disorders

“…Pharmacogenetics investigates the association between genetic markers and the pharmacokinetics and pharmacodynamics of the drug and aims at predicting the individual therapy response based on these associations ( Valdes and Yin, 2016 ). In recent times, advances have been made in neuropsychiatry regarding the understanding of the role of genetic polymorphisms in therapy response to treatment approaches as in major depressive disorder ( Shalimova et al, 2021 ), schizophrenia ( Jovanović et al, 2010 ), or epilepsy ( Al-Eitan et al, 2020 ). The role of pharmacogenetics for therapy success with compounds used for the treatment of headache disorders is not as largely investigated, and pharmacogenetic information is hitherto practically not used to predict efficacy or adverse effects in clinical practice in this field ( Christensen et al, 2016 ).…”