文章摘要
朱明媚,景 霞,孙 芳,湛 雯.CYP2C9、CYP2A6基因多态性对丙戊酸钠血药浓度的影响[J].南京医科大学学报,2017,(1):40~43
CYP2C9、CYP2A6基因多态性对丙戊酸钠血药浓度的影响
Effects of CYP2C9 and CYP2A6 genetic polymorphisms on plasma concentrations of sodium valproate
投稿时间:2016-05-24  
DOI:10.7655/NYDXBNS20170108
中文关键词: 丙戊酸钠  CYP2C9  CYP2A6  基因多态性  血药浓度
英文关键词: sodium valproate  CYP2C9  CYP2A6  polymorphisms  plasma concentration
基金项目:南京医科大学科技发展基金面上项目(2013NJMU117)
作者单位
朱明媚 南京医科大学附属儿童医院药学部江苏 南京 210008 
景 霞 南京医科大学附属儿童医院药学部江苏 南京 210008 
孙 芳 南京医科大学附属儿童医院药学部江苏 南京 210008 
湛 雯 南京医科大学附属儿童医院药学部江苏 南京 210008 
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中文摘要:
      目的:研究CYP2C9、CYP2A6基因多态性对癫痫患儿丙戊酸钠血药浓度的影响。方法:收集单用丙戊酸钠治疗的癫痫患儿,应用荧光偏振免疫法测定丙戊酸钠血药浓度;分别采用直接测序法、巢式PCR法检测CYP2C9、CYP2A6的基因型;应用单因素方差分析研究基因多态性对丙戊酸钠血药浓度的影响。结果:83例癫痫患儿根据CYP2C9、CYP2A6基因型分为3组:强代谢组(CYP2C9*1*1合并CYP2A6*1*1)、中代谢组(CYP2C9*1*3合并CYP2A6*1*1或CYP2C9*1*1合并CYP2A6*1*4)和弱代谢组(CYP2C9*1*3合并CYP2A6*1*4或CYP2A6*4*4),3组分布频率分别为73.5%、24.1%和2.4%。中代谢组的标准化血药浓度显著高于高代谢组(P<0.05),低代谢组的标准化血药浓度均数比其他两组高,但差异无统计学意义(P>0.05)。结论:CYP2C9、CYP2A6的基因多态性能影响丙戊酸钠血药浓度,可通过检测基因型选择合适的丙戊酸钠初始剂量。
英文摘要:
      Objective: To investigate the effects of CYP2C9 and CYP2A6 genetic polymorphisms on plasma concentrations of sodium valproate (VPA) in the epileptic children. Methods: Epileptic children treated with sodium valproate only were collected in our study. Fluorescence polarization immunoassay was performed to measure plasma concentrations of sodium valproate. Direct sequencing and nest-PCR were applied to identify the genotypes of CYP2C9 and CYP2A6. One-way ANOVA was performed to analyze the influence of the polymorphisms on plasma concentrations of sodium valproate. Results: Patients were divided into 3 groups according to the genotypes of CYP2C9 and CYP2A6: extensive metabolizers (EM, CYP2C9*1*1 & CYP2A6*1*1), intermediate metabolizers (IM, CYP2C9*1*3 & CYP2A6*1*1 or CYP2C9*1*1 & CYP2A6*1*4), and poor metabolizers (PM, CYP2C9*1*3 & CYP2A6*1*4 or CYP2A6*4*4), and the frequencies of the three groups were 73.5%, 24.1%, and 2.4%, respectively. The standardized blood drug concentration of IM was significantly higher than that of EM (P<0.05). The mean of standardized blood drug concentration of PM was higher than the others, but there were no significant differences between them (P>0.05). Conclusion: The plasma concentrations of sodium valproate can be affected by the polymorphisms of CYP2C9 and CYP2A6. Clinicians can choose appropriate initial dosage by detecting the genotypes.
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