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9938866 
Journal Article 
Effects of major transporter and metabolizing enzyme gene polymorphisms on carbamazepine metabolism in Chinese patients with epilepsy 
Zhu, X; Yun, W; Sun, X; Qiu, F; Zhao, L; Guo, Y 
2014 
1 
Pharmacogenomics
ISSN: 1462-2416 
15 
15 
1867-1879 
English 
25495409 
AIM: The present study aimed to evaluate the effects of SNPs of major transporter and metabolizing enzyme genes on carbamazepine (CBZ) metabolism in Chinese patients with epilepsy.

MATERIALS & METHODS: For 210 epileptic patients treated with CBZ as monotherapy, nine SNPs in candidate genes ABCB1, CYP3A4, CYP3A5, POR and EPHX1 were analyzed by PCR-RFLP or direct sequencing. Serum concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC. Dose-adjusted concentrations of CBZ (CDRCBZ), CBZE (CDRCBZE), CBZD (CDRCBZ D) and CBZD:CBZE ratio were used as evaluation parameters for CBZ metabolism.

RESULTS: The ABCB1 c.3435C>T was significantly associated with the CDR of CBZ and its major metabolites. CYP3A4*1G and CYP3A5*3 could influence CBZ metabolism, while POR*28 had no effect on it. The EPHX1 c.416A>G and c.128G>C variants were significantly associated with CBZD:CBZE ratio.

CONCLUSION: Our data suggest that certain polymorphisms of major transporter and metabolizing enzyme genes could in part influence interindividual variability of CBZ metabolism in Chinese patients with epilepsy.