Association between <i>ABCB1</i> polymorphisms and response to first-generation antiepileptic drugs in a Tunisian epileptic population

Ajmi, Mohamed; Boujaafar, Sana; Zouari, N.; Amor, Dorra; Asma, Nasr; Rejeb, N.; Amor, Sana Ben; Omezzine, Asma; Benammou, S.; Bouslama, Ali

doi:10.1080/00207454.2017.1412964

Cited by 21 publications

(36 citation statements)

References 76 publications

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“…Epileptic syndromes represented only 26% of our epileptic patients, in fact that most of our patients with isolated seizures have no EEG results or have an EEG with no specific electroclinical syndrome. This result is similar to another study from the center of Tunisia (18.3%) [32]. The etiology remained unknown in 57% of our cases, in drug-resistant patients and drug-responsive ones (52% and 62%).…”

Section: Discussionsupporting

confidence: 92%

“…In accordance with epilepsy type, drug-resistant and drug-responsive patients showed a predominance of generalized seizures (84% vs. 66%), compared to focal (6% vs. 34%) and focal to bilateral tonic-clonic seizures (10% vs. 0%). Some studies provided the same results [74, 76, 77], while many others showed the opposite [32, 73, 75, 78–82] due to some changes recently made in the classifications of epilepsies taken into account the type of onset seizures [32, 56]. Epileptic syndromes represented only 26% of our epileptic patients, in fact that most of our patients with isolated seizures have no EEG results or have an EEG with no specific electroclinical syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies suggested that its altered function could be a result of genetic variants especially SNPs located in the ABCB1 gene [4, 17–25]. The most studied SNPs in this gene are C1236T (rs1128503) in exon 12, G2677T (rs2032582) in exon 21, and C3435T (rs1045642) in exon 26 [26–32].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the fact that there was a significant interest in showing the associations between drug resistance and ABCB1 3435 genotypes, the clinical practice of a ABCB1 SNPs routine testing to predict the patient's response to the therapy has not been yet examined [32, 49, 54]. Therefore, we focus, in this work, on evaluating the relationship between the ABCB1 C1236T, G2677T, and C3435T polymorphisms and the pharmacoresistant epilepsy in Tunisian patients.…”

Section: Introductionmentioning

confidence: 99%

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ABCB1 Polymorphisms and Drug-Resistant Epilepsy in a Tunisian Population

et al. 2019

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Background Epilepsy is one of the most common neurological disorders with about 30% treatment failure rate. An interindividual variations in efficacy of antiepileptic drugs (AEDs) make the treatment of epilepsy challenging, which can be attributed to genetic factors such as ATP-Binding Cassette sub-family B, member1 (ABCB1) gene polymorphisms. Objective The main objective of the present study is to evaluate the association of ABCB1 C1236T, G2677T, and C3435T polymorphisms with treatment response among Tunisian epileptic patients. Materials and Methods One hundred epileptic patients, originated from north of Tunisia, were recruited and categorized into 50 drug-resistant and 50 drug-responsive patients treated with antiepileptic drugs (AEDs) as per the International League Against Epilepsy. DNA of patients was extracted and ABCB1 gene polymorphisms studied using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results The C1236T, G2677T, and C3435T polymorphisms were involved into AED resistance. Significant genotypic (C1236T TT (p ≤ 0.001); G2677T TT (p = 0.001); C3435T TT (p ≤ 0.001)) and allelic associations (C1236T T (3.650, p ≤ 0.001); G2677TT (1.801, p = 0.044); C3435T T (4.730, p ≤ 0.001)) with drug resistance epilepsy (DRE) were observed. A significant level of linkage disequilibrium (LD) was also noted between ABCB1 polymorphisms. Patients with the haplotypes CT and TT (C1236T-G2677T); GT, TC, and TT (G2677T-C3435T); CT and TT (C1236T-C3435T); CTT, TTC, TGT, and TTT (C1236T-G2677T-C3435T) were also significantly associated to AED resistance. Conclusions The response to antiepileptics seems to be modulated by TT genotypes, T alleles, and the predicted haplotypes for the tested SNPs in our population. Genetic analysis is a valuable tool for predicting treatment response and thus will contribute to personalized medicine for Tunisian epileptic patients.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ABCB1 Polymorphisms and Drug-Resistant Epilepsy in a Tunisian Population

et al. 2019

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“…ABCC2 rs717620 -24 CT+TT genotypes and ABCC2 rs3740066 (3972C>T) CT+TT genotypes are overrepresented in epileptic patients resistant to antiepileptic drugs in the Chinese population, whereas ABCC2 rs2273697 (1249G>A) and ABCB1 rs1045642 (3435C>T) polymorphisms were not found to be associated with drug-resistant epilepsy in this population. The frequency of the haplotype TGT (ABCC2 -24C>T/ABCC2 1249G>A/ABCC2 3972C>T) in resistant patients is double that of responsive patients [309]. The TAGAA haplotype in CACNA1A accumulates in drug-resistant patients in the Chinese population [310].…”

Section: Epilepsymentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6–10 drugs/day with the consequent risk for drug–drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 geno-phenotypes are involved in the metabolism of over 90% of drugs currently used in patients with dementia, and only 20% of the population is an extensive metabolizer for this tetragenic cluster. ADRs associated with anti-dementia drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, and antiepileptic drugs can be minimized by means of pharmacogenetic screening prior to treatment. These drugs are substrates, inhibitors, or inducers of 58, 37, and 42 enzyme/protein gene products, respectively, and are transported by 40 different protein transporters. APOE is the reference gene in most pharmacogenetic studies. APOE-3 carriers are the best responders and APOE-4 carriers are the worst responders; likewise, CYP2D6-normal metabolizers are the best responders and CYP2D6-poor metabolizers are the worst responders. The incorporation of pharmacogenomic strategies for a personalized treatment in dementia is an effective option to optimize limited therapeutic resources and to reduce unwanted side-effects.

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