Genetic variations associated with pharmacoresistant epilepsy (Review)

Abstract

epilepsy is a common, serious neurological disorder worldwide. although this disease can be successfully treated in most cases, not all patients respond favorably to medical treatments, which can lead to pharmacoresistant epilepsy. drug-resistant epilepsy can be caused by a number of mechanisms that may involve environmental and genetic factors, as well as disease-and drug-related factors. in recent years, numerous studies have demonstrated that genetic variation is involved in the drug resistance of epilepsy, especially genetic variations found in drug resistance-related genes, including the voltage-dependent sodium and potassium channels genes, and the metabolizer of endogenous and xenobiotic substances genes. The present review aimed to highlight the genetic variants that are involved in the regulation of drug resistance in epilepsy; a comprehensive understanding of the role of genetic variation in drug resistance will help us develop improved strategies to regulate drug resistance efficiently and determine the pathophysiological processes that underlie this common human neurological disease. Contents 1. introduction 2. Pharmacoresistant epilepsy 3. Genetic variations associated with pharmacoresistant epilepsy 4. The role of genetic variants in the diagnosis and treatment of pharmacoresistant epilepsy 5. clinical implications of genetic variants in pharmacoresistant epilepsy 6. conclusions and future perspectives noeMÍ cÁrdenaS-rodrÍGueZ 1

Nonsyndromic Early-Onset Epileptic Encephalopathies: Two Novel <b><i>KCTD7</i></b> Pathogenic Variants and a Literature Review

“…In the 21st century, a new terminology has been introduced “developmental and epileptic encephalopathy.” The International League Against Epilepsy (ILAE) Classification of the epilepsies revision has been highly notable as this appropriate term can be used for individuals of any age. Review of studies showed that there has not been much for onset age, but it seems that occurrence in the most critical period of brain maturation such as during infancy and early childhood is considerably destructive [2-5], the insight that prompted us to emphasize on it in the current research and name our patients’ disease name.…”

Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review

“…The genetic variants hypothesis states that polymorphisms are associated with pharmacodynamics, metabolic pathways, enzymes, ion channels and neurotransmitter receptors, block drug binding, metabolism and transport. Most commonly, there are: gene 1 of subfamily B of ATP-binding cassette (ABCB1 or MDR1) and subfamily C of ATP-binding cassette (ABCC2 or MRP2), subunits 1, 2 and 3 of potential-dependent sodium channels (SCN)-SCNα (SCN1, SCN2 and SCN3); metabolizers of endogenous and xenobiotic substances, cytochrome P450 families 2 and 3 (CYP2 and CYP3), genes for acetylcholine receptors, neural potassium channels, calcium channels and GABA receptors [76]. Recent data supports the important role of genetics in patients with untreatable seizures.…”

Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters

“…An ABCB1 SNP, rs2032582 (AT and AG), had no clear relationship with VPA and CBZ resistance. ABCB1 1199G>A (rs2229109) polymorphism was frequently found in VPA-related ADRs; in particular, the rs2032582 TA and rs2229109 GA genotypes showed the highest incidence of ADRs and could be identified as the strongest risk factors [ 134 , 135 , 136 ].…”

“…ABCC2 −24T allele carriers were at higher risk of anticonvulsant failure probably because of an ABCB1 up-regulation; however, the exact mechanisms are still unknown. There were no associations between the presence of an ABCC2 1249G>A variant and CBZ response [ 135 , 136 , 137 , 138 ]. In addition, the presence of G allele and the GG genotype at the g.‒1774delG locus of ABCC2 resulted in neurological adverse VPA reactions, especially tremor.…”