Maleki Mehri, Sayyah Mohammad, Kamgarpour Fatemeh, Karimipoor Morteza, Arab Aida, Rajabi Anahita, Gharagozli Kourosh, Shamshiri Ahmad Reza, Shahsavand Ananloo Esmaeil
Dept. of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Dept. of Genetics, Faculty of Basic Sciences, Tarbiat Modares University, TehranIran, Iran.
Iran Biomed J. 2010 Jul;14(3):89-96.
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.
三分之一的癫痫患者对多种抗癫痫药物（AED）耐药。P-糖蛋白（P-gp）是一种由ATP结合盒亚家族B成员1（ABCB1）基因编码的外排转运蛋白，可将药物排出细胞，在AED耐药中起重要作用。P-gp的过度表达可能是ABCB1基因多态性的结果。我们研究了伊朗癫痫患者中ABCB1基因的T129C和T1236C单核苷酸多态性（SNP）与耐药性癫痫的关联。
从200名健康对照者和332名癫痫患者中获取DNA样本，其中200名对药物有反应，132名耐药。通过聚合酶链反应随后进行限制性片段长度多态性分析来确定这两个SNP的基因型频率。
在成人和儿童中，均未发现T129C和T1236C基因型与耐药性癫痫之间存在显著关联。然而，1236CC（P = 0.02）或CT（P = 0.008）基因型的女性患者比TT基因型的女性患者耐药风险更高。有症状性癫痫且基因型为1236CC（P = 0.02）或CT（P = 0.004）的患者比TT基因型的患者耐药风险也更高。特发性癫痫且基因型为129TT（P = 0.001）的患者比CT基因型的患者耐药风险更低。
我们的结果表明，T1236C多态性与伊朗女性癫痫患者的耐药性有关。需要进行大样本量的重复研究来证实我们的结果。
