CYP2C19基因多态性与丙戊酸血药浓度相关性及个体化用药研究

Study on correlation between CYP2C19 gene polymorphism with serum valproic acid concentration and individualized medication

目的观察分析CYP2C19基因多态性与癫痫患者丙戊酸血药浓度的个体差异,并为临床个体化用药提供参考依据。方法选取2015年1月至2016年12月于该院就诊的癫痫患者148例,采用实时荧光聚合酶链反应(PCR)技术检测148例患者的CYP2C19基因分型,同时给予丙戊酸治疗,分析CYP2C19基因多态性与丙戊酸血药浓度的相关性。结果不同CYP2C19基因型的癫痫患者丙戊酸血药浓度存在很大的个体差异,其中148例癫痫患者等位基因和基因型分布频率比较,差异无统计学意义(P>0.05);CYP2C19*2位点的AA基因型服药2、4、8h后丙戊酸血药浓度水平显著高于CYP2C19*2位点GG基因型,差异有统计学意义(P<0.05);CYP2C19*3位点AA基因型服药8h后丙戊酸血药浓度水平显著高于8h后丙戊酸血药浓度水平CYP2C19*3位点GG基因型,差异有统计学意义(P<0.05);其他基因型丙戊酸血药浓度水平比较,差异无统计学意义(P>0.05)。结论癫痫患者的CYP2C19基因具有多态性,且与服用丙戊酸治疗的癫痫患者血液浓度具有相关性。因此,在采用丙戊酸治疗癫痫患者时,可检测患者CYP2C19基因分型,以指导癫痫患者的临床个体化治疗。

Objective To observe and analyze the difference of CYP2C19 gene polymorphism and serum alproic acid concentration in the patients with epilepsy to provide reference for clinical individualized medica-ion. Methods A total of 148 patients with epilepsy in the hospital from January 2015 to December 2016 were elected and their CYP2C19 genotypes were detected by adopting the real-time fluorescence polymerase chain eaction,meanwhile the cases were given the valproic acid treatment. Then the correlation between CYP2C19 ene polymorphism and serum valproic acid concentration was analyzed. Results There was great individual differences in serum valproic acid concentration difference among CYP2C19 genotypes, in which the alleles and enotypes distribution frequency had no statistically significant difference among 148 cases of epilepsy （P^〉 . 05） ;Serum valproic acid concentrations at 2,4,8 h after medication in the patients with AA genotype at CYP2C19 ＊ 2 locus were significantly higher than those in the patients with GG genotype at CYP2C19 ＊ 2 lo-us, the difference was statistically significant（P〈C0. 05） ;Serum valproic acid concentrations at 8 h after medi-ation in the patients with AA genotype at CYP2C19 ＊ 3 was significantly higher than that in the patients with GG genotype at CYP2C19 ＊ 3 locus,the difference was statistically significant （P〈C0. 05） ;Serum valproic acid oncentration had no statistically significant difference among other genotypes（P〉0. 05）. Conclusion The CYP2C19 gene in the patients with epilepsy has polymorphism,moreover which is correlated with the patient’s blood concentration of vaproic acid. Therefore ？ treating the patients with epilepsy by using valproic acid can detect the CYP2C19 genotyping in the patients in order to guide their individualized treatment.