Mehri Maleki1,2, Mohammad Sayyah3, Fatemeh Kamgarpour1,4, Morteza Karimipoor1, Aida Arab1, Anahita Rajabi1, Kourosh Gharagozli5, Ahmad Reza Shamshiri6, Esmaeil Shahsavand Ananloo7. 1. Dept. of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. 2. Dept. of Genetics, Faculty of Basic Sciences, Tarbiat Modares University, TehranIran, Iran. 3. Dept. of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran. 4. Dept. of Cell and Molecular Biology, Khatam University, Tehran, Iran. 5. Dept. of Neurology, Loghman Hospital, Shahid Beheshti University of Medical Sciences, Tehran, iran. 6. Dept. of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 7. Dept. of Genomic Psychiatry, Roozbeh Hospital, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND: One third of epileptic patients are resistant to several anti-epileptic drugs (AED). P-glycoprotein (P-gp) is an efflux transporter encoded by ATP-binding cassette subfamily B member 1 (ABCB1) gene that excludes drugs from the cells and plays a significant role in AEDs resistance. Over-expression of P-gp could be a result of polymorphisms in ABCB1 gene. We studied the association of T129C and T1236C single-nucleotide polymorphisms (SNP) of ABCB1 gene with drug-resistant epilepsy in Iranian epileptics. METHODS: DNA samples were obtained from 200 healthy controls and 332 epileptic patients, of whom 200 were drug responsive and 132 drug resistant. The frequencies of the genotypes of the two SNP were determined by polymerase chain reaction followed by restriction fragment length polymorphism. RESULTS: No significant association was found between T129C and T1236C genotypes and drug-resistant epilepsy neither in adults nor in children. However, the risk of drug resistance was higher in female patients with 1236CC (P = 0.02) or CT (P = 0.008) genotype than in those with TT genotype. The risk of drug resistance was also higher in patients with symptomatic epilepsies with 1236CC (P = 0.02) or CT (P = 0.004) genotype than in those with TT genotype. The risk of drug resistance was lower in patients with idiopathic epilepsies with 129TT genotype (P = 0.001) than in those with CT genotype. CONCLUSION: Our results indicate that T1236C polymorphism is associated with drug resistance in Iranian female epileptic patients. Replication studies with large sample sizes are needed to confirm our results.
BACKGROUND: One third of epilepticpatients are resistant to several anti-epileptic drugs (AED). P-glycoprotein (P-gp) is an efflux transporter encoded by ATP-binding cassette subfamily B member 1 (ABCB1) gene that excludes drugs from the cells and plays a significant role in AEDs resistance. Over-expression of P-gp could be a result of polymorphisms in ABCB1 gene. We studied the association of T129C and T1236C single-nucleotide polymorphisms (SNP) of ABCB1 gene with drug-resistant epilepsy in Iranian epileptics. METHODS: DNA samples were obtained from 200 healthy controls and 332 epilepticpatients, of whom 200 were drug responsive and 132 drug resistant. The frequencies of the genotypes of the two SNP were determined by polymerase chain reaction followed by restriction fragment length polymorphism. RESULTS: No significant association was found between T129C and T1236C genotypes and drug-resistant epilepsy neither in adults nor in children. However, the risk of drug resistance was higher in female patients with 1236CC (P = 0.02) or CT (P = 0.008) genotype than in those with TT genotype. The risk of drug resistance was also higher in patients with symptomatic epilepsies with 1236CC (P = 0.02) or CT (P = 0.004) genotype than in those with TT genotype. The risk of drug resistance was lower in patients with idiopathic epilepsies with 129TT genotype (P = 0.001) than in those with CT genotype. CONCLUSION: Our results indicate that T1236C polymorphism is associated with drug resistance in Iranian female epilepticpatients. Replication studies with large sample sizes are needed to confirm our results.
Entities:
Keywords:
ATP-binding cassette subfamily B member 1; Drug-resistant epilepsy; Single nucleotide polymorphism
Authors: Areej M Al Qahtani; Ayat B Al-Ghafari; Huda A Al Doghaither; Anas H Alzahrani; Ulfat M Omar; Sawsan A Rahimulddin Journal: Afr Health Sci Date: 2019-09 Impact factor: 0.927
Authors: Ayat B Al-Ghafari; Areej M Al Qahtani; Suzan N Alturki; Huda A Al Doghaither; Ekramy M Elmorsy; Hanaa M Tashkandi; Atlal M Abusanad; Shadi S Alkhayyat; Ulfat M Omar; Ahmed A Zeeneldin Journal: Oncol Lett Date: 2020-08-24 Impact factor: 2.967