Influence of CYP Gene Polymorphism on Sodium Valproate levels And Clinical Outcome in Pediatric Epilepsy:A Cohort Study

ABSTRACT: Introduction: One of the metabolic processes of sodium valproate (SV) metabolism is cytochrome P450 (CYP)-mediated oxidation. Polymorphisms in the genes encoding CYP enzymes can cause changes in SV concentration and clinical outcome. The study's goal of the study was to explore the pattern of CYP gene polymorphisms in pediatric epileptics in terms of sodium valproate concentration and clinical outcome. Methodology: Ninety-nine pediatric epileptics aged 2 to 18 years who were receiving Sodium Valproate monotherapy were included in this cohort study. PCR-RFLP was used to examine the genetic polymorphism patterns of CYP2C9 and CYP3A4. HPLC was used to estimate the serum valproate concentration at the trough level. SPSS 23 examined the relationship between SV concentration and CYP genotypes. ANOVA test was utilized, and a P-value of 0.05 was regarded as statistically significant. Results: PCR-RFLP showed GG wild type (37.3%), mutant GA (46.6%), AA (16.1%) in CYP3A4 (G331A) and CC wild type(90%,) mutant carrier type, CT (10%) in CYP2C9 (C430T). The mean serum valproate concentration observed was 105.40 ± 49.9 μg/ml. There was no statistically significant difference between the gene polymorphism of CYP3A4 (G331A) and CYP2C9 (C375T) with sodium valproate concentration. The SNPs were not in equilibrium. Conclusion: There was no significant difference in the serum concentration of sodium valproate in different CYP3A4 and CYP2C9 gene variants. Though statistically insignificant, patients with wild type of CYP2C9 had a higher relative risk of bad clinical compared to other patterns . The study may be of great use in personalized therapy in pediatric epilepsy.

ORGANISM(S): Homo sapiens (human)

SUBMITTER:  

PROVIDER: S-BSST865 | biostudies-other |

SECONDARY ACCESSION(S): S-EPMC6266652

REPOSITORIES: biostudies-other