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CYP2C9 (*2&*3) and CYP2C19 (*2&*3) polymorphisms among children with nonlesional epilepsy: a single-center study

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Abstract

Cytochrome (CYP) P450 enzymes are responsible for metabolism of antiepileptic drugs (AEDs), and encoded by highly polymorphic genes. A case–control study was conducted in Mansoura University Children’s Hospital, Egypt including 100 children with nonlesional epilepsy (50 AEDs responders and 50 resistant cases) and 50 healthy controls. All participants were investigated for frequencies of CYP2C9 (*2&*3) and CYP2C19 (*2&*3) genotypes and alleles using polymerase chain reaction. The current study reported higher frequencies of CYP2C9*2 (CT) genotype and (T) allele among responsive and resistant groups than controls (P < 0.001). Frequency of (TT) genotype was higher in resistant than responsive group (P = 0.02, OR 12, 95% CI 1.2–122.3). No significant differences were detected between responsive and resistant groups regarding CYP2C9*2 alleles (P = 0.2). CYP2C9*3 (AC) genotype was more frequent in controls than other groups (P < 0.001). No significant differences were detected between responsive and resistant groups regarding neither CYP2C9*3 genotypes nor alleles (P = 0.11 and 0.2, respectively). CYP2C19*2&*3 (GA) genotypes and (A) alleles were more frequent in responsive and resistant groups than controls (P < 0.001). No significant differences were detected between responsive and resistant groups regarding neither CYP2C19*2&*3 genotypes nor alleles (P = 0.21 and 0.89 for CYP2C19*2; P = 1 and 0.77 for CYP2C19*3). The CYP2C9*2 (TT) genotype, earlier seizure onset and higher seizures frequency were associated with higher risks of refractory epilepsy. We concluded that heterozygous genotypes of CYP2C9*2 and CYP2C19 (*2&*3) and mutant alleles of studied variants were more frequent among children with nonlesional epilepsy. CYP2C9*2 (TT) genotype increased refractory epilepsy susceptibility.

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Availability of data and material

The datasets generated during the current study are available in the Mendeley Data: http://dx.doi.org/10.17632/z8432k2bg6.1.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt

    Samah Eltalal, Mostafa El Ayouty & Yahya Wahba

  2. Biochemistry Section, Mansoura University Children’s Hospital, Mansoura, Egypt

    Afaf El-Said

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by SE and YW. AE performed the molecular work-up. The first draft of the manuscript was written by YW, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yahya Wahba.

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All procedures involving human participants were in accordance with the ethical standards of Institutional Research Board of Medical Faculty of Mansoura University, Egypt (Code No: MS/954) and the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Written informed consents were taken from caregivers of all study participants.

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Eltalal, S., El Ayouty, M., El-Said, A. et al. CYP2C9 (*2&*3) and CYP2C19 (*2&*3) polymorphisms among children with nonlesional epilepsy: a single-center study. Acta Neurol Belg 121, 1623–1631 (2021). https://doi.org/10.1007/s13760-020-01442-y

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