Influence of UGT1A3 Polymorphism on Sodium Valproate Monotherapy And Clinical Outcome in Pediatric Epileptic Patients: A Cohort study

Abstract

Objective: The objective of this study was to assess the association between UGT1A3 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy.

Methodology: This Prospective Cohort study recruited hundred Pediatric epileptic patients in the age group of 2-18 years, receiving sodium valproate as monotherapy at least for 1 month. Blood sample were collected after obtaining consent for genetic polymorphism analysis, to estimate serum drug concentration and biochemical parameters and for platelet estimation. Genomic DNA from whole blood was isolated by Phenol-chloroform extraction and ethanol precipitation method which was then processed for amplification by PCR followed by Sequencing method for mutation analysis. Biochemical investigations were performed by hematology cell counter. Clinical outcome was assessed in terms of efficacy and safety of sodium valproate.

Results: It was observed that majority of wild varieties of A17G and C133T suffered either with GTCS or partial seizures suggesting that the mutation would be beneficial in reducing the risk of seizures. Vice versa holds good for T31C, G81A, T140C and A477G. Patients with mutant varieties were epileptic in these genotypes suggesting that these mutations were dangerous. There was no significant difference in the liver function tests at Basal, 6 months and 1 year as well as between the genotypes. Even though serum creatinine levels were in the biological reference range. There was no significant association between gene polymorphisms and serum VPA concentrations, though VPA levels were significantly different in different intervals.

Conclusion: UGT1A3 gene polymorphism studies may be used before initiating sodium valproate treatment to predict the treatment response. The drug was well tolerated in our study population without much change in hepatic, renal, and pancreatic parameters. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective anti-epileptic drug.