Chbili Chahra, Fathallah Neila, Laouani Aicha, Nouira Manel, Hassine Anis, Ben Amor Sana, Ben Ammou Sofiene, Ben Salem Chaker, Saguem Saad
a Metabolic Biophysics, Professional Toxicology and Applied Environmental Laboratory, Department of Biophysics, Medicine Faculty of Sousse , Sousse University , Sousse , Tunisia ;
b Department of Pharmacovigilance, Faculty of Medicine of Sousse , Sousse University , Sousse , Tunisia ;
J Neurogenet. 2016 Mar;30(1):16-21. doi: 10.3109/01677063.2016.1155571.
The aim of this study was to evaluate the impact of polymorphisms in the EPHX1 (c.416A > G, c.337T > C) and CYP3A422 genes involved in carbamazepine (CBZ) metabolism and pharmacoresistance among 118 Tunisian patients with epilepsy under maintenance dose of CBZ. These genetic polymorphisms were analyzed by PCR-RFLP. Associations between plasma CBZ concentration, CBZ-E concentration, maintenance doses and metabolic ratio (CBZ-E:CBZ, CBZ-D:CBZ-E) were analyzed with each polymorphism. Both variants of EPHX1 c.416A > G and c.337T > C are significantly associated with higher metabolic ratio CBZ-E:CBZ and seem to decrease the activity of the epoxide hydrolase. The CYP3A422 variant allele is significantly associated with lower CBZ-D:CBZ-E ratio and seems also to be associated with less activity of the cytochrome. Our data suggest that certain polymorphisms of metabolizing enzyme genes could influence inter-individual variability of CBZ metabolism.
本研究的目的是评估参与卡马西平（CBZ）代谢和耐药性的EPHX1基因（c.416A＞G、c.337T＞C）和CYP3A422基因多态性对118例接受CBZ维持剂量治疗的突尼斯癫痫患者的影响。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析这些基因多态性。分析每种多态性与血浆CBZ浓度、CBZ-E浓度、维持剂量和代谢率（CBZ-E:CBZ、CBZ-D:CBZ-E）之间的关联。EPHX1基因的c.416A＞G和c.337T＞C两种变体均与较高的CBZ-E:CBZ代谢率显著相关，似乎会降低环氧化物水解酶的活性。CYP3A422变异等位基因与较低的CBZ-D:CBZ-E比率显著相关，似乎也与细胞色素活性较低有关。我们的数据表明，代谢酶基因的某些多态性可能会影响CBZ代谢的个体间差异。
