CYP2C19基因多态性对肺结核患者利福平血药浓度的影响及个体化用药的研究

Influence of Genetic Polymorphism of CYP2C19 on Rifampicin Individual Dosage Regimen in Pulmonary Tuberculosis Patients

目的探讨肺结核患者给予利福平(RFP)后血药浓度的个体差异与肝药酶P450 2C19(CYP2C19)基因多态性的关系,为临床合理用药提供参考。方法 HPLC检测142例肺结核患者利福平的血药浓度。运用PCR-RFLP方法对所有患者的CYP2C19*2和CYP2C19*3位点进行基因型分型,分析基因多态性与RFP血药浓度的相关性。结果不同基因型的肺结核患者RFP血药浓度在个体间存在很大差异,其中CYP2C19*2位点的AA基因型与GG基因型的患者相比,给药后2、4、8 h前者RFP血药浓度明显高于后者,差异有统计学意义(P<0.05);CYP2C19*3位点的AA基因型与GG基因型的患者相比,给药后8 h前者RFP血药浓度明显高于后者,差异有统计学意义(P<0.05),其他基因型之间比较差异无统计学意义(P>0.05)。结论本研究结果证实CYP2C19基因多态性影响RFP血药浓度,说明药物遗传学因素对RFP临床合理用药有指导意义。

Objective To investigate the genetic polymorphism of CYP2C19 on the interindividual variation of rifampicin concentration in pulmonary tuberculosis patients and provide reference for rational medication in clinic.Methods Rifampicin Concentration in blood plasma were determined by HPLC in 142 pulmonary tuberculosis patients,CYP2C19 variants were detected using PCR-RELP method and futher studied the relationship between CYP2C19 polyphism and plasma concentration of RFP.Results Rifampicin Conclusion had great interindividual variation in different genotypes.RFP plasma concentration after administration 2 h,4 h and 8 h were significantly higher in CYP2C19 ＊2 AA homozygote than in CYP2C19 ＊2 GG homozygote.RFP plasma concentration after administration 8h were significantly higher in CYP2C19 ＊3 AA homozygote than in CYP2C19 ＊3 GG homozygote.Among other genotypes were not found statistical significance.Conclusion The data suggest that CYP2C19 polymorphism signifiantly impacts the concentration of RFP,and the pharmacogenomics is important to rationalize the medication of RFP.