ABCB1 Polymorphisms and Drug-Resistant Epilepsy in a Tunisian Population. (2nd December 2019)

• Record Type: Journal Article
• Authors: Chouchi, Malek; Klaa, Hedia; Ben-Youssef Turki, Ilhem; Hila, Lamia
• Other Names: Chace Donald H. Academic Editor.
• Is Part Of: Disease markers. Volume 2019(2019)
• Publication Date: 2019-12-02
• Subjects: Diagnosis -- Periodicals; Biochemical markers -- Periodicals; Pathology -- Periodicals; 616
• DOI: 10.1155/2019/1343650
• Languages: English
• ISSNs: 0278-0240

Abstract

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.