An association between the rs1799853 and rs1057910 polymorphisms of CYP2C9, the rs4244285 polymorphism of CYP2C19 and the prevalence rates of drug-resistant epilepsy in children

Abstract

Objective

Epilepsy is a neurologically based disease. Literature data indicate a certain association between the polymorphism of these genes, which participate in the metabolism of drugs (CYP), and drug-resistant epilepsy.

Aim

The reports describe studies in which an association was evaluated between the rs1799853 (430C > T) and rs1057910 (1075A > C) polymorphisms of CYP2C9 gene and the rs4244285 (c.681G > A) polymorphism of CYP2C19 gene on one hand and the incidence of drug-resistant epilepsy in children on the other.

Material and methods

The above-mentioned polymorphisms were assessed by the PCR-RFLP technique in a group of patients with drug-resistant (n = 106) and drug-responsive (n = 80) epilepsy, as well as in non-epileptic children (n = 97), all of them hospitalised at the Department of Neurology of the Institute-Polish Mother’s Memorial Hospital in Lodz.

Results

It was demonstrated that CT genotype of the rs1799853 polymorphism of CYP2C9 gene and GA genotype of the rs4244285 polymorphism of CYP2C19 gene caused an enhanced risk of epilepsy. It was also shown that the occurrence of C-G-A haplotype, when referred to the rs1799853 polymorphism of CYP2C9 gene and the rs4244285 polymorphism of CYP2C19 gene, could be associated with a decreased risk of epilepsy occurrence. In case of the rs1799853 polymorphism in CYP2C9 gene, the occurrence of T allele four times increases the risk of drug-resistance in patients with diagnosed epilepsy.

Conclusion

The obtained results indicated that the rs1799853 and rs1057910 polymorphisms of CYP2C9 gene and the rs4244285 polymorphism of CYP2C19 gene could be associated with the occurrence of drug-resistant epilepsy in children.

Keywords:

• Drug-resistant epilepsy
• CYP2
• gene
• polymorphism

Acknowledgments

Authors acknowledge the financial support provided by the Institute of Polish Mother’s Memorial Hospital, Lodz, Poland, to conduct the study. Thank the professor M. Stasiołek for help in collecting research material.

Disclosure Statement

Authors declare no conflict of interest.

Author Beata Smolarz declares that she has no conflict of interest. Author Marianna Makowska declares that she has no conflict of interest. Author Magdalena Bryś declares that she has no conflict of interest. Author Ewa Forma declares that she has no conflict of interest. Author Hanna Romanowicz declares that she has no conflict of interest.

Authors’ contributions

Conceived and designed the experiments: MM, BS. Performed the experiments – case group: EF, MB. Case group design and collect: MM, HR. Performed the experiments – control group: BS, HR. Analysed data: MM, BS, HR. Contributed reagents/materials/analysis tools MB, EF. Contributed to the writing of manuscript: BS, MM. All authors approved the final manuscript.

Compliance with ethical standards

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.

Ethics approval

All the study participants gave a written informed consent. 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).

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).

Consent for publication

Not applicable, the manuscript doesn’t contain any individual person’s data.

Availability of data and material

Data will not be shared, because it is part of a clinical database.

Additional information

Funding

This work was supported by the Institute of Polish Mother’s Memorial Hospital, Lodz, Poland from the Statutory Development Fund.