中文摘要：

目的：阐明中国人群癫痫患者CYP2C19和CYP2C9的基因多态性对丙戊酸清除率的影响。方法：收集216例癫痫患者的一般生物学资料和临床常规监测的丙戊酸（VPA）稳态血药浓度（谷浓度）数据。提取血样中白细胞的DNA并进行PCR扩增，用限制性片断长度多态性技术（RFLP）分别检测CYP2C19和CYP2C9的基因型。依据不同的基因型．将病人分为3组：G1、G2和G3。G1组：野生型；G2组：突变杂合型；G3组：突变纯合型。分别求算3组患者稳态血药谷浓度与每日公斤体重药量的比值。即丙戊酸的清除率。采用多元回归分析法推算不同基因型对丙戊酸清除率的影响。结果：216例病人中，G1、G2、G3组人数分别为86、86、44。3组患者稳态血药谷浓度分别为：（54．13±21．53）、（54．43±18．86）、（62．55±25．62）μmL；清除率分别为（11．49±4．47）、（11．13±4．95）、（9．40±4．67）mL·h^-1·kg^-1。每种基因型均和丙戊酸的清除率具有相关性。采用多元回归分析求得回归方程为：G1组：Y=7．395＋0．299mg·kg^-1·d^-1；G2组：Y=4．503＋0．473mg^-1·kg^-1·d^-1；G3组：Y=5．025＋0．335mg·kg^-1·d^-1。CYP2C19和CYP2C9的不同基因型对丙戊酸清除率的影响具有统计学意义且G3组患者的清除率明显低于G1组和G2组。结论：CYP2C19、CYP2C9的基因型对丙戊酸的清除率有影响，突变纯合型患者丙戊酸的清除率明显低于野生型和突变杂合型的患者，应依据基因型进行个体化用药。

英文摘要：

AIM： To evaluate the effects of CYP2C19 and CYP2C9 gene polymorphisms on Valproate （VPA） clearance of epileptic patients in China in order to promote individualized medicine. METHODS： The demographic data and steady plateau concentrations of VPA from 216 epileptic patients to tetrospectively collected. The gene polymorphisms of CYP2C19 and CYP2C9 were examined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. According to the genotype of CYP2C19 and CYP2C9, these patients were divided into three groups： G1 （wild type）, G2 （ heterozygous type）, G3 （ homozygous type）. The mean of VPA oral clearance （CL/F） was calculated for each group, and was compared among three groups. The relationship between mean of VPA oral clearance and gene polymorphism was characterized by multiple regression analysis. RESULTS： In 216 cases of Chinese patients, the number of patients in each group was 86 （G1）, 86 （G2） and 44（G3）. The mean plateau concentrations in three groups were （54.13 ± 21.53）, （54.43 ± 18.86）,（62.55 ± 25.62） μg/mL, and CL/F of VPA were （11.49 ± 4.47）, （11.13 ± 4.95）, （9.40 ± 4.67） mL· h^-1·kg^-1, respectively. The CL/F of VPA in G3 group was lower than those in the other two groups. There was significant correlation between genotype and VPA oral clearance. The regression equation were as following： G1 group： Y=7.395 ＋0.299 mg^-1·kg^-1·d^-1, G2 group： Y = 4.503 ＋ 0.473 mg^-1·kg^-1·d^-1; G3 group： Y = 5.025 ＋ 0.335 mg^-1·kg^-1·d^-1. CONCLUSION： The polymorphisms of CYP2C19 and CYP2C9 have effects on the VPA oral clearance. The CL/F of VPA in homozygous type is significantly lowered than one in heterozygous type. It will be valuable to facilitate individualized usage of VPA according to the genotype in clinical therapy.