engleski

ABCB1 gene variants as predictors of multidrug- resistant epilepsy in Croatian population

P-glycoprotein (Pgp) is a drug efflux transporter and is the encoded product of the human multidrug resistance gene ABCB1 (MDR1). Pgp is expressed in the blood-brain barrier (BBB) and blood- cerebrospinal fluid (CSF) barrier, and reduces the brain penetration of antiepileptic drugs (AEDs). Functional polymorphism or overexpression of Pgp in the BBB of patients with epilepsy may play a role in pharmacoresistance. The aim of this study was to investigate the possible association of ABCB1 gene polymorphisms C1236T in exon 12, G2677T in exon 21, and C3435T in exon 26 with the development of resistance to antiepileptic therapy. All patients enrolled in the study had an established diagnosis of partial complex epilepsy with or without secondary generalisation and have been suffering from it for more than two years. Patients were devided into two groups. The first group comprised 57 patients refractory to the current therapy, while group 2 consisted of 48 patients with well-controled seizures. Results of our study showed statistically significant difference in the allele and genotype frequency of ABCB1 G2677T between resistant and nonresistant patients. Haplotype G2677/C3435/C1236 was overrepresented among resistant patients. According to our results, ABCB1 variants C1236T, G2677T and C3435T might be associated with therapeutic response to AED in patients with partial epilepsy with or without secondary generalization and represent a possible predictive factor for pharmacoresistance.

ABCB1 gene ; epilepsy ; multi-drug resistance ; polymorphism

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