Polymorphisms of ABCG2, ABCB1 and HNF4α are associated with Lamotrigine trough concentrations in epilepsy patients

Lamotrigine (LTG) is commonly used to control seizure in epilepsy patients and with referenced therapeutic windows in clinical practice. This study is to identify and characterize the function of genetic variants that influence the trough concentrations of LTG in epilepsy patients following monotherapy regimen (37.5-250 mg/d). Twelve single nucleotide polymorphisms (SNPs) involved in LTG metabolism and transport pathways, including UGT2B7, ABCB1, ABCG2, NR1I2 and HNF4 alpha were genotyped in 140 Chinese epilepsy patients. Steady-state trough concentration of LTG was measured by a high-performance liquid chromatography method. Polymorphisms in ABCG2 rs2231142, rs3114020, HNF4 alpha rs2071197 and ABCB1 rs1128503 were found to be associated with LTG CDR (concentration/dose normalized by body weight). In addition, multiple linear regression analysis revealed that ABCG2 rs2231142 had a remarkable effect on LTG concentrations which is stated to be 4.8% of the variability of LTG and may also help to interpret ethnic difference in LTG pharmacokinetics. Our findings provided new insights that SNPs of genes involved in the transport of LTG contribute to interpatient variation in LTG pharmacokinetics. Future studies are necessary to determine whether these SNPs can be used to provide LTG dosing guidance and influence seizure control and adverse reaction of LTG. Copyright (C) 2015, Published by Elsevier Ltd on behalf of The Japanese Society for the Study of Xenobiotics.