Relationship between ABCB1 3435TT genotype and antiepileptic drugs resistance in Epilepsy: updated systematic review and meta-analysis

Chouchi, M.; Kaabachi, Wajih; Klaa, Hédia; Tizaoui, Kalthoum; Turki, Ilhem Ben-Youssef; Hila, Lamia

doi:10.1186/s12883-017-0801-x

Cited by 70 publications

(40 citation statements)

References 99 publications

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“…Many further single and multiple SNP-based associations were published of different patient groups, varying case and control definitions, and, generally, small sample sizes. Some studies supported the original association, whereas others did not; meta-analyses of many such studies remain equivocal (Haerian et al, 2011;Sun et al, 2014;Chouchi et al, 2017), but it is still the case that the correctly designed, adequately controlled, and credibly powered study has not yet been undertaken. There are no common genetic variants associated with drug resistance currently in use to predict this phenotype.…”

Section: F Gene Variant Hypothesismentioning

confidence: 99%

Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options

et al. 2020

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Significance Statement-Drug resistance provides a major challenge in epilepsy management. Here, we will review the current understanding of the molecular, genetic, and structural mechanisms of drug resistance in epilepsy and discuss how the problem might be overcome. 608 Löscher et al. Adapted from Rogawski and Löscher (2004), Rogawski et al. (2016), and Sills and Rogawski (2020) Molecular target ASDs that act on target Voltage-gated ion channels Voltage-gated sodium channels Phenytoin, fosphenytoin, a carbamazepine, oxcarbazepine, b eslicarbazepine acetate, c lamotrigine, lacosamide; possibly topiramate, zonisamide, rufinamide Voltage-gated calcium channels (T-type) Ethosuximide Voltage-gated potassium channels (K v 7) Retigabine (ezogabine) GABA-mediated inhibition GABA A receptors Phenobarbital, primidone, stiripentol, benzodiazepines, (including diazepam, lorazepam, midazolam and clonazepam), possibly topiramate, felbamate, retigabine (ezogabine) GAT1 GABA transporter Tiagabine GABA transaminase Vigabatrin Glutamic acid decarboxylase Possibly valproate, gabapentin, pregabalin Presynaptic release machinery SV2A Levetiracetam, brivaracetam a2d subunit of calcium channels Gabapentin, pregabalin Ionotropic glutamate receptors AMPA receptor Perampanel Carbonic anhydratase inhibition Acetazolamide, topiramate, zonisamide, possibly lacosamide Disease-specific mTORC1 signaling d Everolimus Lysosomal enzyme replacement e Cerliponase alfa (recombinant tripeptidyl peptidase 1) Mixed/unknown Valproate, felbamate, topiramate, zonisamide, rufinamide, adrenocorticotrophin (ACTH), cannabidiol, cenobamate AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate. a Fosphenytoin is a prodrug for phenytoin. b Oxcarbazepine serves largely as a prodrug for licarbazepine, mainly S-licarbazepine. c Eslicarbarbazepine acetate is a prodrug for S-licarbazepine. d In patients with epilepsy because of tuberous sclerosis complex (TSC). e In patients with epilepsy because of neuronal ceroid lipofuscinosis type 2.

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Section: F Gene Variant Hypothesismentioning

confidence: 99%

Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options

et al. 2020

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“…These varied results of studies that involved different ethnic groups or races should consequently consider the study of ABCB1 haplotype or diplotype that represents the functional unit of the gene [11]. Meanwhile, a systematic review and metaanalysis of 13 studies involving a total of 454 patients with AED-resistant epilepsy and 282 response-to-AEDs indicated that TT genotype of ABCB1 C3435T played an important role in the incidence of refractory epilepsy [49].…”

Section: Resultsmentioning

confidence: 99%

Allele Frequency of Carbamazepine Major Efflux Transporter Encoding Gene ABCB1 C3435T among Javanese-Indonesian Population

Istikharah¹,

Hartienah²,

Vitriyani³

et al. 2020

Open Access Maced J Med Sci

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BACKGROUND: Genetic variations in ABCB1 gene that encodes P-glycoprotein, the main transporter in the efflux of carbamazepine (CBZ) from the brain cells, can lead to pharmacodynamic and pharmacokinetic variability. Polymorphism of C3435T is widely known to cause protein overexpression that contributes to an increased risk of CBZ resistance. AIM: This study determined the allele frequency distribution of ABCB1 C3435T gene in healthy subjects of the Javanese population as a major ethnic group in Indonesia. METHODS: This cross-sectional study involved 100 healthy volunteers who fulfilled the inclusion criteria. The genotype analysis to detect polymorphism in the targets employed the polymerase chain reaction-restriction fragment length polymorphism method with 5’-TGCTGGTCCTGAAGTTGATCTGTGAAC-3’ as the forward primer and 5’-ACATTAGGCAGTGACTCGATGAAGGCA-3’ as the reverse primer. RESULTS: The frequency of subjects with C allele in ABCB1 C3435T gene reached 53%, higher than that with T allele. CONCLUSION: This finding was nearly the same as that in studies of the populations in China, Turkey, and four countries in the South European continent. It is recommended to conduct further research on the correlation between C3435T polymorphism and CBZ dose variability to provide a comprehensive approach to epilepsy management in patients receiving CBZ.

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“…Most recent studies continue to provide evidence of significant associations between drug resistance and ABCB1 3435 genotypes [36] . In addition, the results of a recent meta-analysis indicates that ABCB1 C3435T polymorphism, especially TT genotype, plays an important role in refractory epilepsy; the authors suggest that genetic screening of this genotype, before starting the treatment, may be useful to predict AED response [37] . Studies of gene variants for other transporter proteins such as multidrugresistanceassociated protein 2 (MRP2)/ABCC2 failed to provide evidence for a clinical impact of these tests in epilepsy therapy [38,39] .…”

Section: Pharmacoresistancementioning

confidence: 99%

Personalized medicine in epilepsy patients

Orsini¹,

Esposito²,

Perna³

et al. 2018

JTGG

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The large number of different syndromes and seizure types together with an interindividual variable response to antiepileptic drugs (AEDs) make the treatment of epilepsy challenging. Fortunately, the last few years have been characterized by a huge interest in epilepsy genetics and two methods, genome-wide analyses and next-generation sequencing, have definitely given the possibility to write a new chapter in the book of treatment of epilepsy, the chapter on precision medicine. Epilepsy offers a good opportunity for the personalization of therapy if we consider that at least one third of epileptic patients do not achieve complete seizure control with the currently available pharmacological treatments, treatment is still often empirical and precise therapy, based on the pathogenesis and the mechanism of each AED is not generally possible because this mechanism often remains incompletely known. In addition, new drugs are often not targeted but developed using in vivo seizure models, to be potentially used by the largest number of patients. This method leads to a therapy aimed at treating the symptoms and the seizures rather than the single pathogenic mechanism of each seizure type or syndrome. In this narrative review, we summarize the established evidence regarding pharmacogenomics in epilepsy and discuss the basis of precision medicine.

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Relationship between ABCB1 3435TT genotype and antiepileptic drugs resistance in Epilepsy: updated systematic review and meta-analysis

Cited by 70 publications

References 99 publications

Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options

Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options

Allele Frequency of Carbamazepine Major Efflux Transporter Encoding Gene ABCB1 C3435T among Javanese-Indonesian Population

Personalized medicine in epilepsy patients

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