Association between ABCB1 polymorphisms and response to first-generation antiepileptic drugs in a Tunisian epileptic population
| Autor: | Marwa Ajmi, Sofien Benammou, Sana Ben Amor, Nabila Ben Rejeb, Ali Bouslama, Asma Nasr, Asma Omezzine, Dorra Amor, Nadia Zouari, Sana Boujaafar |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Linkage disequilibrium ABCB1 gene Tunisia Adolescent Population Drug resistance Gastroenterology Polymorphism Single Nucleotide 03 medical and health sciences Epilepsy Young Adult 0302 clinical medicine Age Distribution Gene Frequency Internal medicine medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Allele education Child Genotyping education.field_of_study business.industry General Neuroscience Infant Newborn Infant General Medicine Middle Aged medicine.disease First generation 030104 developmental biology Treatment Outcome Pharmacogenetics Child Preschool Anticonvulsants Female business 030217 neurology & neurosurgery |
| Zdroj: | The International journal of neuroscience. 128(8) |
| ISSN: | 1563-5279 |
| Popis: | We aimed in this study to investigate the association between the ATP-Binding Cassette sub-family B, member1 (ABCB1) polymorphisms: C1236T (rs1128503), G2677T (rs2032582) and C3435T (rs1045642), and the resistance to antiepileptic drugs (AEDs).The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism genotyping of ABCB1 polymorphisms was conducted on 153 Tunisian epileptic patients treated with AEDs.Two genetic polymorphisms of the ABCB1 gene seemed to influence the response to AEDs. In fact, the G2677T T and the C3435T T alleles appeared to increase the risk of developing AEDs resistance (ORs* = 3.13; 95%CI = [1.16-8.98]; p = 0.024 and ORs* = 3.10; 95%CI = [1.15-8.37]; p = 0.025), respectively. However, the C1236T T allele did not seemed to influence the response to AEDs (ORs* = 1.14; 95%CI = [0.53-3.88]; p = 0.471). Haplotypic analysis indicated high-degree linkage disequilibrium of ABCB1 polymorphisms. Our results showed a synergic effect, in fact patients with the CTT and TTT haplotypes were more likely to be drug resistant than patients with the CGC haplotype, these associations remained significant even after adjustment for confounding parameters (ORs* = 2.68; 95%CI = [1.11-8.25]; p = 0.033 and ORs* = 3.76; 95%CI = [1.69-21.05]; p = 0.006, respectively).The G2677T T and C3435T T alleles as well as the TT, CTT and TTT haplotypes seemed to be significantly associated with drug-resistance epilepsy in our population. Genetic predisposition, involved in this resistance, may contribute to the establishment of a personal optimized therapy for newly diagnosed epileptic patients. |
| Databáze: | OpenAIRE |
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