ABCB1 Polymorphisms and Drug-Resistant Epilepsy in a Tunisian Population

• Published in: Disease markers Vol. 2019; no. 2019; pp. 1 - 16
• Main Authors: Hila, Lamia, Ben Youssef Turki, Ilhem, Klaa, Hedia, Chouchi, Malek
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2019; Hindawi; Hindawi Limited
• Subjects: Acids; Age; Age of Onset; Anticonvulsants - therapeutic use; Antiepileptic agents; ATP Binding Cassette Transporter, Subfamily B - genetics; Case-Control Studies; Child; Child, Preschool; Convulsions & seizures; Deoxyribonucleic acid; DNA; Drug resistance; Drug Resistant Epilepsy - drug therapy; Drug Resistant Epilepsy - genetics; Drugs; Epilepsy; Etiology; Failure rates; Family medical history; Female; Gene polymorphism; Genetic analysis; Genetic Association Studies; Genetic factors; Genotypes; Haplotypes; Humans; Intellectual disabilities; Linkage Disequilibrium; Male; Males; Metabolism; Neurological diseases; Patients; Polymerase chain reaction; Polymorphism; Polymorphism, Restriction Fragment Length; Population; Population genetics; Precision medicine; Restriction fragment length polymorphism; Single-nucleotide polymorphism; Studies; Tunisia; Tunisia
• ISSN: 0278-0240; 1875-8630
• DOI: 10.1155/2019/1343650

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.