The Associations Between Genetic Polymorphisms And Plasma Lamotrigine Concentrations In Epilepsy Patients

ObjectiveTo investigate the effects of OCT1, ABCG2, ABCC2 and HNF4oc genetic polymorphisms on plasma Lamotrigine (LTG) concentrations and therapeutic efficacy in Chinese patients with epilepsy.MethodsThe study cohort comprised 112 Han Chinese patients with epilepsy who were receiving LTG monotherapy in the Second Affiliated Hospital of Zhejiang University School of Medicine. The doses were recorded and blood samples were taken, and normalized LTG concentrations were adjusted by doses and body weights. The polymorphisms of OCT1 rs2282143, rs628031, ABCG2 rs2231142, rs2231137, ABCC2 rs2273697 and HNF4a rs2071197, rs3212183 were determined. The therapeutic efficacy of LTG at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. The genotype distributions were assessed and the associations between genetic polymorphisms and plasma Lamotrigine concentrations and therapeutic efficacy were analyzed.ResultsAll the genotype frequencies of OCT1, ABCG2, ABCC2 and HNF4a were consistent with Hardy-Weinberg equilibrium. There were significant associations between OCT1 rs628031, ABCG2 rs2231142 polymorphisms and normalized LTG concentrations in patients with epilepsy (P<0.05). However, polymorphisms of OCT1 rs2282143, ABCG2 rs2231137, ABCC2 rs2273697 and HNF4a rs2071197, rs3212183 exhibited no association with LTG concentrations. In addition, no significant differences exist between genotypes of OCT1, ABCG2, ABCC2 and HNF4oc polymorphisms and LTG treatment response.ConclusionThese results suggested that the polymorphisms of OCT1 rs628031 and ABCG2 rs2231142 may affect LTG metabolism in Chinese patients with epilepsy. Therefore, future genetic screening may help provide individualized diagnosis and treatment in clinical practice.