CYP2C9 (*2&*3) and CYP2C19 (*2&*3) Polymorphisms Among Children with Nonlesional Epilepsy: a Single-center Study

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.