Effects of UGT1A3, UGT1A6, and UGT2B7 genetic polymorphisms on plasma concentration of valproic acid in south Chinese epilepsy patients

Valproic acid (VPA) is one of the most commonly used anti-epileptic drugs in epilepsy patients. The large interindividual variability in plasma VPA concentration may reflect functional consequence of genetic polymorphisms in genes encoding drug-metabolizing enzymes, especially uridine 5’-diphospho (UDP)-glucuronosyltransferase (UGT). This study was aimed to determine the relationship between plasma VPA concentration and the polymorphisms of UGT1A3, UGT1A6 and UGT2B7 in south Chinese patients with epilepsy. UGT1A3, UGT1A6 and UGT2B7 polymorphisms were identified by polymerase chain reaction-ligase detection reaction (PCR-LDR) in 97 epileptic treated with VPA monotherapy. The steady-state plasma concentrations of VPA were measured by High Performance Liquid Chromatography (HPLC) and associated with UGT1A3, UGT1A6 and UGT2B7 polymorphisms. The UGT1A3 A17G polymorphism showed a significant influence, with higher VAP Cs in carrier of AA genotype than in AG genotype (P = 0.034). For UGT1A3 C133T, significant difference in VAP Cs were detected between carriers of CC and CT genotypes, with higher VAP Cs in carrier of CC genotype than in CT genotype (P = 0.016). For UGT1A6 A552C, patients who were carriers of AA and AC genotypes were characterized with a significant higher VAP Cs than carrier of CC genotype. Therefore, these results suggest that the polymorphisms of UGT1A3 A17G, UGT1A3 C133T and UGT1A6 A552C in epilepsy patients may affect VPA concentration.