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Prevalence of UGT1A6 polymorphisms in children with epilepsy on valproate monotherapy

Puneet Jain, Shivaram Shastri, Sheffali Gulati1

  • 1Department of Pediatrics, Division of Pediatric Neurology, All India Institute of Medical Sciences, New Delhi, India.

Neurology India
|March 10, 2015
PubMed

Insights

Genetic variations in UGT1A6 were analyzed in Indian children with epilepsy. Due to a small sample size, the direct impact of these UGT1A6 polymorphisms on valproate levels could not be reliably determined.

Area of Science:

  • Pharmacogenetics
  • Clinical Pharmacology
  • Epilepsy Research

Background:

  • Valproate is a widely used anticonvulsant medication.
  • Uridine 5΄-diphospho (UDP)-glucuronosyltransferase (UGT) enzymes metabolize approximately 50% of valproate.
  • Genetic variations (polymorphisms) in UGT enzymes may explain differing valproate levels in epilepsy patients.

Purpose of the Study:

  • To investigate the genetic polymorphisms of UGT1A6 in Indian children diagnosed with epilepsy.
  • To assess the potential influence of UGT1A6 genetic variations on valproate pharmacokinetics in this pediatric population.

Main Methods:

  • A cross-sectional study involving 80 Indian children (aged 3-12 years) with epilepsy on valproate monotherapy.
  • UGT1A6 polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed with genetic sequencing.
  • Steady-state plasma valproate concentrations were measured using High Performance Liquid Chromatography (HPLC).

Main Results:

  • Prevalence data for UGT1A6 T19G, A541G, and A552C polymorphisms were established in the study cohort.
  • The study population included TT (45%), TG (38.8%), GG (16.3%) for T19G; AA (48.8%), AG (38.8%), GG (12.5%) for A541G; and AA (43.8%), AC (40%), CC (16.3%) for A552C.
  • A reliable association between UGT1A6 genotypes and valproate dosage or serum concentration was not achievable due to the limited sample size.

Conclusions:

  • The study successfully reported the frequencies of UGT1A6 genotypes and alleles in Indian children with epilepsy.
  • Further research with larger cohorts is needed to establish the clinical significance of UGT1A6 polymorphisms on valproate pharmacokinetics.
Abstract

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