ABCB1 Polymorphisms and Drug-Resistant Epilepsy in a Tunisian Population

Abstract

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.

Clinical Efficacy Evaluation and Potential Mechanism of Zhishe Tongluo Capsule in the Treatment of Cerebral Infarction by Meta-Analysis Associated with Network Pharmacology

“…Cerebral infarction is a serious neurological disease, and Chinese medicine belongs to the category of “stroke.” Cerebral infarction, also known as ischemic stroke or cerebral embolism, is one of the commonest cerebrovascular diseases [ 28 ]. The prevalence of cerebral infarction is high, accounting for 75%–80%.…”

Multi‐omic strategies applied to the study of pharmacoresistance in mesial temporal lobe epilepsy

“…Finally, replication is still lacking for both clinical and preclinical studies. Unfortunately, the initial progress in the genetic studies of pharmacoresistance in epilepsy was hampered by the controversy involving the putative association of a specific polymorphism in the ABCB1 gene with pharmacologic response in patients with epilepsy, 30,[32][33][34][35][36][37][38]167 which recent larger studies and meta-analyses have refuted. 39,[168][169][170][171] Our view on this matter is that even if there is an influence of ABCB1 in pharmacoresistance, the effect is most likely small and insufficient to influence the phenotype alone.…”

Impact of ABCB1 Polymorphisms on Lacosamide Serum Concentrations in Uygur Pediatric Patients With Epilepsy in China

“…2 However, approximately 25%–30% of patients with epilepsy fail to become seizure free or become resistant to treatment and, as a result, experience recurrent seizures. 3 …”

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