Association Analysis Of P-glycoprotein Expression And Drug-resistant Epilepsy In Patients With Epilepsy

Background: Epilepsy is one of the most frequent neurologic disorders, affectingapproximately1%～2%of the world population. In around20%～30%of the patients withepilpsy, the condition is refractory to medical treatment. Characterized by high morbidity andmortality, pharmacoresistant forms of epilepsy remain a major health problem despiteadvances in antiepileptic pharmacotherapy and new antiepileptic drugs (AEDs) developed inthe last two decades. Most patients with epilepsy who are resistant to one major AED are alsorefractory to other AEDs, although the drugs act by different mechanisms. The realpathological mechanism of drug resistance remains obscure in spite of numerous studiesconducted, but a decreased AEDs uptake into the brain is suspected to play a role.P-glycoprotein (P-gp), a transmembrane transporter encoded by ATP-binding cassettesubfamily B member1(ABCB1) gene and located at the endothelial cells of the blood-brainbarrier (BBB), may be associated with epilepsy pharmacoresistance.Objective: To explore the relationship between P-gp expression in serum andcerebrospinal fluid in patients with epilepsy and epilepsy drug-resistance, and analyze thecorrelation between that expression and ABCB1gene C3435T SNPs in patients with epilepsy.Materials and methods:187cases patients with epilepsy were collected in the study,which included100cases drug-resistant patients with epilepsy and87cases drug responsivepatients with epilepsy. Adopt Enzyme-linked immunosorbent assay (ELISA) method tomeasure the concentration of P-gp in serum and cerebrospinal fluid. Results: The concentration of P-gp in cerebrospinal fluid of the drug-resistant group aswell as the two ratio of the concentration between the serum and the cerebrospinal fluid werehigher than the responsive group, had a statistically significant difference (P<0.05). The P-gpconcentration in cerebrospinal fluid of the patients with epilepsy with the ABCB1C3435Tgene CC genotype were higher than the CT and TT genotype, the TT genotype was minimum,there existed significant differences (P<0.05).Conclusion: The overexpression of p-gp in patients with epilepsy cerebrospinal fluidhad a close relationship with the epilepsy drug-resistance. The SNPs at C3435T of ABCB1inpatients with epilepsy could affect the P-gp level concentration in the cerebrospinal fluid, andP-gp was highly expressed in the cerebrospinal fluid of patients with epilepsy carrying theCC genotype.