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Associations between MDR1 C3435T polymorphism and drug-resistant epilepsy in the Polish population

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Abstract

Epilepsy is a common neurological disorder. About one-third of epileptic patients demonstrate multidrug resistance (MDR) phenotype and develop drug-resistant epilepsy (DRE). Single nucleotide polymorphism (SNP) C3435T (rs1045642), identified in the MDR1 gene, is associated with an increased intestinal expression of P-glycoprotein (P-gp) which affects the levels of anti-epileptic drugs in plasma. The reported study was designed to explore associations between the MDR1-C3435T gene SNP and the risk of DRE in the Polish population. The C3435T polymorphism of MDR1 gene was investigated by the PCR-RFLP technique in 74 patients with DRE and 70 age- and sex-matched non-DRE controls. Blood samples were obtained from patients with drug-resistant epilepsy, treated at the Department of Neurological Surgery, Medical University in Warsaw between the years 2011 and 2012. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for each genotype and allele. Genotype distribution of C3435T polymorphism of MDR1 gene was compared between the DRE patients and controls with significant differences (p < 0.05) between the two investigated groups. A possible association was observed between DRE and the presence of 3435C allele. The 3435C allele was found in 69 % of DRE cases and in 48 % of the used controls. The variant 3435T allele of MDR1 decreased the risk of drug-resistant epilepsy [odds ratio (OR) 0.41; 95 % confidence interval (CI) 0.26–0.67]. The results indicate that the C3435T polymorphism of MDR1 gene may be associated with the incidence of DRE observed in the Polish population.

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Acknowledgments

The authors acknowledge the financial support provided by the Institute of Polish Mother’s Memorial Hospital, Lodz, Poland, to conduct the study and Warsaw University of Medical Sciences, Warsaw, Poland, for their clinical support.

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Authors and Affiliations

  1. Department of Neurology, Regional Hospital. Dr. Charles Jonscher, Lodz, Poland

    Dominik Skalski

  2. Department of Neurology, TriMedic Medical Center, Lodz, Poland

    Janusz Wendorff

  3. Department of Clinical Pathomorphology, Polish Mother’s Memorial Hospital-Research Institute, Lodz, Poland

    Hanna Romanowicz

  4. Department of Neurological Surgery, Medical University, Warsaw, Poland

    Andrzej Rysz & Andrzej Marchel

  5. Department of Neurology, Polish Mother’s Memorial Hospital-Research Institute, Lodz, Poland

    Mariusz Stasiołek

  6. Laboratory of Cancer Genetics, Department of Clinical Pathomorphology, Polish Mother’s Memorial Hospital-Research Institute, Rzgowska 281/289, 93-338, Lodz, Poland

    Beata Smolarz

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  1. Dominik Skalski
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  2. Janusz Wendorff
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  3. Hanna Romanowicz
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Correspondence to Beata Smolarz.

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Conflict of interests

The authors declare no conflict of interest as regards the reported study.

Ethical approval

This work was supported by the Institute of Polish Mother’s Memorial Hospital, Lodz, Poland from the Statutory Development Fund. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study. A formal consent was also issued by the Bioethical Committee of the Institute of the Polish Mother’s Memorial Hospital in Lodz (Approval number, 15.12.2010).

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Skalski, D., Wendorff, J., Romanowicz, H. et al. Associations between MDR1 C3435T polymorphism and drug-resistant epilepsy in the Polish population. Acta Neurol Belg 117, 153–158 (2017). https://doi.org/10.1007/s13760-016-0690-6

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  • DOI: https://doi.org/10.1007/s13760-016-0690-6

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