The potential implication of SCN1A and CYP3A5 genetic variants on antiepileptic drug resistance among Egyptian epileptic children

Fotoh, Wafaa Moustafa M. Abo El; naby, Sameh abd Allah Abd el; Habib, Mona Salah El‐din; ALrefai, Abeer Ahmed; Kasemy, Zeinab A.

doi:10.1016/j.seizure.2016.07.005

Cited by 58 publications

(18 citation statements)

References 46 publications

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“…This finding was confirmed by Kumari et al (68) in another study with 402 epilepsy patients from the same geographic region. Although Lakhan et al and Kumari et al did not reveal an association between SCN1A c.3184 A>G SNP and ASD resistance, Abo El Fotoh et al (69) demonstrated a significant relationship between the AG genotype or G allele and ASD resistance in Egyptian children with epilepsy.…”

Section: Potential Mechanisms Of Asd Resistancementioning

confidence: 95%

“…On the other hand, the association between IVS5-91G>A in the SCN1A gene and ASD response was not observed in this study (64). Several more recent studies explored the relationship between other SNPs in the sodium channel genes and drug response in epilepsy, including SCN1A c.3184 A>G (rs2298771) and SCN2A c.56 G>A (rs17183814), both of which were found to be functionally significant in some neurological disorders (67–69). In a study including 336 epilepsy patients from the northern part of India, Lakhan et al (67) reported a significant association between the variant allele frequency of SCN2A c.56 G>A SNP and ASD resistance.…”

Section: Potential Mechanisms Of Asd Resistancementioning

confidence: 99%

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Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

2017

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Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy.

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Section: Potential Mechanisms Of Asd Resistancementioning

confidence: 95%

Section: Potential Mechanisms Of Asd Resistancementioning

confidence: 99%

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

2017

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“…A missense mutation in SCN1A leads to dysfunction of inhibitory GABAergic neurons, resulting in brain hyperexcitability and seizures in infants [5]. Mutations in the SCN1A gene lead to severe forms of epilepsy such as Dravet syndrome, or milder forms such as generalized epilepsy with febrile seizures plus (GEFS+), simple febrile seizures and also a non-epileptic condition, familial hemiplegic migraine [6].…”

Section: Introductionmentioning

confidence: 99%

“…Apart from their role in epileptogenesis, the voltage-gated sodium channels also play a major role as antiepileptic drug (AED) targets [6,7]. SCN1A is a target of several AEDs, with some studies demonstrating an association between the SCN1A c.3184A > G/p.…”

Section: Introductionmentioning

confidence: 99%

“…SCN1A is a target of several AEDs, with some studies demonstrating an association between the SCN1A c.3184A > G/p. Thr1067Ala polymorphism and drug resistance [6,7]. SCN1A c.3184A > G/p.Thr1067Ala is a missense polymorphism that results in p.Thr1067Ala substitution, which may affect the structurefunction relationship of the channel, leading to misfiring of brain neurons, thereby explaining its association with epilepsy [6].…”

Section: Introductionmentioning

confidence: 99%

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The association of SCN1A p.Thr1067Ala polymorphism with epilepsy risk and the response to antiepileptic drugs in Slovenian children and adolescents with epilepsy

Bertok

Dolžan

Goričar

et al. 2017

Seizure

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The effect of sodium channels on neurological/neuronal disorders: A systematic review

Bagheri

Haddadi

Saki

et al. 2021

Intl J of Devlp Neuroscience

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Neurological and neuronal disorders are associated with structural, biochemical, or electrical abnormalities in the nervous system. Many neurological diseases have not yet been discovered. Interventions used for the treatment of these disorders include avoidance measures, lifestyle changes, physiotherapy, neurorehabilitation, pain management, medication, and surgery. In the sodium channelopathies, alterations in the structure, expression, and function of voltage-gated sodium channels (VGSCs) are considered as the causes of neurological and neuronal diseases. Online databases, including Scopus, Science Direct, Google Scholar, and PubMed were assessed for studies published between 1977 and 2020 using the keywords of review, sodium channels blocker, neurological diseases, and neuronal diseases. VGSCs consist of one α subunit and two β subunits. These subunits are known to regulate the gating kinetics, functional characteristics, and localization of the ion channel. These channels are involved in cell migration, cellular connections, neuronal pathfinding, and neurite outgrowth. Through the VGSC, the action potential is triggered and propagated in the neurons. Action potentials are physiological functions and passage of impermeable ions. The electrophysiological properties of these channels and their relationship with neurological and neuronal disorders have been identified. Subunit mutations are involved in the development of diseases, such as epilepsy, multiple sclerosis, autism, and Alzheimer's disease. Accordingly, we conducted a review of the link between VGSCs and neurological and neuronal diseases. Also, novel therapeutic targets were introduced for future drug discoveries.

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The potential implication of SCN1A and CYP3A5 genetic variants on antiepileptic drug resistance among Egyptian epileptic children

Abstract: Overall, results confirmed the claimed role of SCN1A c.3184 A/G polymorphism in epilepsy and moreover in development of pharmacoresistance among Egyptian epileptic children. CYP3A5*3 variants have no contributing effect on pharmacoresistance among Egyptian epileptic children.

Cited by 58 publications

References 46 publications

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers

The association of SCN1A p.Thr1067Ala polymorphism with epilepsy risk and the response to antiepileptic drugs in Slovenian children and adolescents with epilepsy

The effect of sodium channels on neurological/neuronal disorders: A systematic review

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