Association between ABCB1-T1236C polymorphism and drug-resistant epilepsy in Iranian female patients

• Published in: Iranian biomedical journal Vol. 14; no. 3; pp. 89 - 96
• Main Authors: Maleki, Mehri, Sayyah, Mohammad, Kamgarpour, Fatemeh, Karimipoor, Morteza, Arab, Aida, Rajabi, Anahita, Gharagozli, Kourosh, Shamshiri, Ahmad Reza, Shahsavand Ananloo, Esmaeil
• Format: Journal Article
• Language: English
• Published: Iran Pasteur Institute of Iran 01-07-2010
• Subjects: Adult; Amino Acid Substitution - genetics; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Case-Control Studies; Demography; Drug Resistance - genetics; Epilepsy - genetics; Female; Gene Frequency - genetics; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Iran; Male; Odds Ratio; Original; Polymorphism, Single Nucleotide - genetics; ATP-binding cassette subfamily B member 1; Drug-resistant epilepsy; Single nucleotide polymorphism
• ISSN: 1028-852X; 2008-823X

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.
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.
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.
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.