Zhu Xu, Yun Wenting, Sun Xiaofu, Qiu Feng, Zhao Limei, Guo Yingjie
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Pharmacogenomics. 2014;15(15):1867-79. doi: 10.2217/pgs.14.142.
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.
The ABCB1 c.3435C>T was significantly associated with the CDR of CBZ and its major metabolites. CYP3A41G and CYP3A53 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.
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.
本研究旨在评估主要转运体和代谢酶基因的单核苷酸多态性（SNPs）对中国癫痫患者卡马西平（CBZ）代谢的影响。
对210例接受CBZ单药治疗的癫痫患者，采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）或直接测序法分析候选基因ABCB1、CYP3A4、CYP3A5、POR和EPHX1中的9个SNPs。采用高效液相色谱法（HPLC）测定血清中CBZ、卡马西平-10,11-环氧化物（CBZE）和卡马西平-10,11-反式二氢二醇（CBZD）的浓度。将CBZ的剂量调整浓度（CDRCBZ）、CBZE的剂量调整浓度（CDRCBZE）、CBZD的剂量调整浓度（CDRCBZD）以及CBZD:CBZE比值作为CBZ代谢的评估参数。
ABCB1基因c.3435C>T与CBZ及其主要代谢产物的剂量调整率显著相关。CYP3A41G和CYP3A53可影响CBZ代谢，而POR*28对其无影响。EPHX1基因c.416A>G和c.128G>C变异与CBZD:CBZE比值显著相关。
我们的数据表明，主要转运体和代谢酶基因的某些多态性可能部分影响中国癫痫患者CBZ代谢的个体间差异。
