Effects of EPHX1, SCN1A and CYP3A4 genetic polymorphisms on plasma carbamazepine concentrations and pharmacoresistance in Chinese patients with epilepsy

• The variant EPHX1 c.416A>G genotypes were associated with increased CBZ concentrations in Chinese patients with epilepsy.
• The SCN1A IVS5-91G>A or CYP3A4*1G polymorphism was not associated with increased CBZ concentrations in Chinese patients with epilepsy.
• There were no associations between all the studied genotypes involving EPHX1 c.337T>C, c.416A>G, SCN1A IVS5-91G>A or CYP3A4*1G and pharmacoresistance in our patient cohort.

SummaryThe pharmacokinetics and pharmacodynamics of carbamazepine (CBZ) vary widely among patients with epilepsy. In this study, we sought to investigate the effects of genetic polymorphisms of the microsomal epoxide hydrolase (EPHX1), the sodium channel α subunit type I (SCN1A) and the cytochrome P450 3A4 (CYP3A4) genes on plasma CBZ concentrations and pharmacoresistance in Chinese patients with epilepsy. The EPHX1 c.337T>C, c.416A>G, SCN1A IVS5-91G>A or CYP3A4*1G polymorphisms were detected by polymerase chain reaction–restriction fragment length polymorphism approach or direct DNA sequencing in 83 Chinese patients treated with CBZ monotherapy. Patients with the variant EPHX1 c.416A>G genotypes had higher adjusted plasma CBZ concentrations compared to those with the wild type genotype (P < 0.05). In contrast, the SCN1A IVS5-91G>A and CYP3A4*1G variant alleles had no significant effects on CBZ maintenance doses or adjusted CBZ concentrations. There were no associations between all the studied genotypes involving EPHX1 c.337T>C, c.416A>G, SCN1A IVS5-91G>A or CYP3A4*1G polymorphisms and pharmacoresistance in this patient cohort. These results suggest that the EPHX1 c.416A>G polymorphism affects CBZ metabolism in Chinese patients with epilepsy. However, whether it contributes to CBZ resistance needs to be further investigated in a larger cohort of patients.