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.
Highlights
Epilepsy is one of the prevalent serious neurological disorders [1] affecting approximately 50 million people worldwide [2].During the last years, a large variety of antiepileptic drugs (AEDs) with different mechanisms of action were developed, which makes the epilepsy treatment a big challenge [3,4,5]
We found a significant allelic and genotypic association between C1236T, G2677T, and C3435T polymorphisms and response to AEDs (Figure 1)
We evaluated the association of drug responders and nonresponders with ABCB1 SNPs according to the individual monotherapy, bitherapy, and polytherapy
Summary
Epilepsy is one of the prevalent serious neurological disorders [1] affecting approximately 50 million people worldwide [2].During the last years, a large variety of antiepileptic drugs (AEDs) with different mechanisms of action were developed, which makes the epilepsy treatment a big challenge [3,4,5]. At least one-third of epileptic patients are or become resistant to treatment and experience recurrent seizures [6, 7] This pharmacoresistance depends on several factors primarily age, epileptic etiology, type, and syndrome, AEDs [8]. Several studies focused on identifying the potential genetic markers affecting the pharmacoresistance They provided several genetic variations affecting pharmacokinetics or pharmacodynamics of AEDs. 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, member (ABCB1) gene polymorphisms. 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. Genetic analysis is a valuable tool for predicting treatment response and will contribute to personalized medicine for Tunisian epileptic patients
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