Effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on oxcarbazepine concentrations and therapeutic efficacy in patients with epilepsy.

Abstract

PURPOSE:

The aim of the study is to investigate the effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy.

METHODS:

We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0.

RESULTS:

The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P<0.05). As for UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy.

CONCLUSION:

These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required.

• Authors: Chunhong Shen, Bijun Zhang, Zhirong Liu, Yelei Tang, Yinxi Zhang, Shan Wang, Yi Guo, Yao Ding, Shuang Wang, Meiping Ding
• Journal: Seizure (Seizure) Vol. 51 Pg. 102-106 (Oct 2017) ISSN: 1532-2688 [Electronic] England
• PMID: 28837897 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Chemical References

• ABCB1 protein, human
• ABCC2 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• Anticonvulsants
• HNF4A protein, human
• Hepatocyte Nuclear Factor 4
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins
• Carbamazepine
• UGT2B7 protein, human
• Glucuronosyltransferase
• Oxcarbazepine

Topics

• ATP Binding Cassette Transporter, Subfamily B (genetics)
• Adult
• Anticonvulsants (blood, therapeutic use)
• Asian People (genetics)
• Carbamazepine (analogs & derivatives, blood, therapeutic use)
• Drug Resistance (genetics)
• Epilepsy (blood, drug therapy)
• Female
• Genotype
• Glucuronosyltransferase (genetics)
• Hepatocyte Nuclear Factor 4 (genetics)
• Humans
• Male
• Middle Aged
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins (genetics)
• Oxcarbazepine
• Polymorphism, Single Nucleotide