RRML - Correlation between ABCB1 gene polymorphisms, antiepileptic drug concentrations and treatment response
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Ahead of print DOI:10.2478/rrlm-2018-0012
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Research article

Correlation between ABCB1 gene polymorphisms, antiepileptic drug concentrations and treatment response

Octavia Sabin, Ioana Corina Bocșan, Adrian Trifa, Zoltan Zsigmond Major, Simona Codruta Heghes, Emanuela Brusturean Bota, Anca Dana Buzoianu

Correspondence should be addressed to: Ioana Corina Bocșan

Abstract:

Aim: A possible molecular mechanism of clinically defined multidrug-resistant epilepsy involves drug efflux transporters such as P glycoprotein (P-gp), a member of the ATP- binding cassette subfamily B1 (ABCB1). We have investigated the prevalence of the C3435T, G 2677T/A, and T129C single-nucleotide polymorphisms in the promoter region of MDR1 gene, in Romanian epileptic patients. Methods: 70 epileptic patients evaluated in the Neurology Department of Cluj County Hospital were included in the study. The response to treatment was assessed by reviewing the seizure diaries and the patients were classified as responders or non-responders. Antiepileptic drug (AED) plasmatic concentrations were measured and the patients were divided into 2 groups: first group with AED concentrations in therapeutic range and the second one with sub-optimal AED concentrations. Genotyping the DNA samples, we investigated MDR1 gene polymorphism by polymerase chain reaction (PCR). Results were expressed as genotype and allele frequencies per response group and compared between subgroups. Results: 33 patients (47.14%) were classified as responders, while the remaining 37 patients (52.86%) were classified as non-responders. A comparison of responders and non-responders revealed no significant difference in genotype frequency for any of the three mutations studied. The CT heterozygote for ABCB1 T129C had significantly lower AED concentrations (p=0.041), with no significant difference for the other polymorphisms studied. Conclusions: In our study we found an association of CT variant in ABCB1 C129T with lower AED plasmatic concentrations and no association between ABCB1 variants and the drug responsiveness.

Keywords: MDR1, antiepileptic drugs, polymorphism, non-responders, P-glycoprotein

Received: 3.11.2017
Accepted: 14.3.2018
Published: 4.6.2018

 
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