Abstrakt

Effect of UGT2B7 Gene Polymorphism with Clinical Pediatric Epileptic patients on Sodium Valproate Monotherapy

Nandith PB, Sachidananda Adiga, Usha Adiga, Vijaya Shenoy, Suchetha Kumari, Prashanth Shetty, Shilpa Shetty, Sharmila KP

Background: Pediatric epilepsy comprises of a chronic neurological disorders characterized by recurrent seizure attack. Sodium valproate is one of the common anti-epileptic drugs used in the treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme Uridine 5’-diphospho (UDP) glucuronosyl transferase (UGT) whose genetic polymorphisms may alter clinical outcome. Aim: To find the association between UGT2B7 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Methods and Materials: In this cohort study, 75 pediatric epileptic patients aged 2-18 years receiving sodium valproate monotherapy for past one month were included from Justice K S Hegde Charitable Hospital, Mangalore, India after obtaining informed consent. Genetic polymorphism patterns of UGT2B7 (C161T, A268G, G211T) was evaluated by PCR-RFLP. Clinical outcome was measured in terms of responders and non-responders based on seizure control during the 6 month observation period. Tolerability was measured by estimating the hepatic, renal and other lab parameters. Clinical outcome in different UGT genotypes was compared by Chi square test. P value <0.05 was considered as significant. Results: Out of 75 patients, CC (41.3%), CT (38.7%), TT (20%) pattern was observed in UGT2B7 (C161T) gene, AA(14.7%), AG(42.7%), GG(42.7%) in (A268G) gene and GG(80%), GT(18.7%), TT(1.3%) in (G211T) gene. It was found that there was no statistical difference in clinical outcome with different UGT2B7 genetic polymorphism patterns. Conclusion: We conclude from our study that genetic polymorphism of UGT2B7 doesn’t have any role on the clinical outcome of epilepsy.