回、汉族癫痫患者CYP2C9和CYP2C19基因多态性与苯巴比妥血药浓度的相关性研究  

The genetic polymorphisms of CYP2C9 and CYP2C19 and association between genetic polymorphisms and phenobarbital serum concentration in Hui and Han-nation epilepsy patients

作　　者：齐明山[1] 顾浩[1] 董通[1] 许贤瑞[2] 王燕[1] 张庆[2] 

机构地区：[1]宁夏医科大学,宁夏银川750004 [2]宁夏医科大学总医院神经内科,宁夏银川750004

出　　处：《中风与神经疾病杂志》2011年第9期776-780,共5页Journal of Apoplexy and Nervous Diseases

基　　金：宁夏自然科学基金重点项目(NZ10112);宁夏回族自治区卫生厅重点科研项目(2009038)

摘　　要：目的研究CYP2C9*3和CYP2C19*2的单核苷酸多态性在回、汉族癫痫人群中的分布特点;探讨两种基因型与苯巴比妥血药浓度的关系。方法对宁夏地区回、汉族癫痫患者185例采用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)分析CYP2C9*3和CYP2C19*2基因型,并进行回、汉族间基因型及等位基因频率的比较;应用反相高效液相色谱法(RP-HPLC)测定其中113例单用苯巴比妥患者的血药浓度,再将其标准化后,分析两种基因型与苯巴比妥血药浓度的关系。结果 (1)回、汉族癫痫患者中CYP2C9*3和CYP2C19*2基因型及等位基因频率均无统计学差异(P>0.05)。(2)根据所携带的CYP2C9和CYP2C19突变等位基因的数量,将113例单用苯巴比妥的患者分为强代谢(EM)组、中间代谢(IM)组和弱代谢(PM)组,IM组和PM组苯巴比妥血药浓度明显高于EM组,且突变基因携带数量与血药浓度呈正相关。结论苯巴比妥血药浓度在CYP2C9和CYP2C19变异基因携带者中增高,根据患者CYP2C9和CYP2C19基因型可以预测患者药物浓度,指导临床选择合适的苯巴比妥初始剂量。Objective To investigate the frequency of polymorphism at CYP2C9*3 and CYP2C19*2 in Hui and Han-nation epileptic patients,then to study the relationship between the genotypes and the phenobarbital serum concentration in patients with epilepsy.Methods The peripheral blood samples of 185 epileptic patients were collected to undergo PCR-RFLP to analyse CYP2C9*3 and CYP2C19*2 genotypes,then the alleles frequencies were compared between different nations.RP-HPLC was used to measure the phenobarbital serum concentration of 113 patients who only take phenobarbital,then standardized by dosage and body weight.Results There were no significant differences both in the genotype frequency and allele frequency in CYP2C9*3 and CYP2C19*2 between Hui and Han groups(both P>0.05).The allele variants were classified into 3 groups:estensive metabolizer(EM),intermediate metabolizer(IM),and poor metabolizer(PM).The phenobarbital serum concentration of the PM and IM group was significantly higher than that of the EM group.Conclusion Owing to the CYP2C9 and CYP2C19 genotypes,we can predict phenobarbital serum concentration correctly and choose appropriate phenobarbital doses to minimize the adverse reactions as possible.

关 键 词：抗癫痫药(AEDs) 苯巴比妥 细胞色素 P450(CYP) 基因型 

分 类 号：R742.1[医药卫生—神经病学与精神病学]