摘要
目的探讨CYP2D6和CYP2C19基因多态性与利培酮治疗精神分裂症临床效应个体差异之间的相关性。方法应用聚合酶链反应(PCR)与DNA测序相结合的方法检测精神分裂症患者CYP2D6和CYP2C19基因多态性。应用高效液相色谱分别测定利培酮、9-羟利培酮的血药浓度,以治疗前后阳性和阴性症状量表(PANSS)评分减分率评价药物临床疗效,比较不同基因型之间血药浓度和药物临床疗效的差异。结果55例单用利培酮治疗的精神分裂症患者,CYP2D6(C100T)不同基因型之间利培酮血药浓度分布差异有统计学意义(P<0.05),但该位点与该药的临床效应之间没有相关性(P>0.05)。CYP2C19*2(G681A)基因多态性与利培酮在体内代谢以及该药临床效应之间差异无统计学意义(P>0.05)。结论CYP2D6(C100T)对利培酮血药浓度有影响,但与利培酮的临床效应个体差异间无相关性。CYP2C19*2(G681A)可能不是引起利培酮代谢以及临床效应个体差异的主要因素。
Objective To explore the correlation between CYP2D6, CYP2C19 genetic polymorphisms and the therapeutic response to risperidone on individuals with schizophrenia. Methods Polymerase chain reaction （PCR） and DNA sequencing were used to examine CYP2D6 and CYP2C19 genetic polymorphisms of schizophrenics. Using highperformance liquid chromatography to measure the plasma concentrations of risperidone and 9-hydroxyrisperidone. The clinical effectiveness was evaluated by the reduction of the positive and negative symptom scale （PANSS）. Results There is significant association between the CYP2D6 （C100T） genotypes and the plasma concentration of risperidone, but no correlation between the CYP2D6 （C100T） genotypes and the clinical effectiveness of risperidone on individuals with schizophrenia is found among 55 patients. And there is no association between CYP2C19 ＊ 2 （G681A） genotypes and risperidone response. Conclusion The CYP2D6 （C100T） may affect the metabolism of risperidone, but there is no evidence to show the correlation between the mutation of CYP2D6 （C100T） and the clinical effectiveness of risperidone on individuals with schizophrenia. CYP2C19 ＊ 2 （G681A） may have no impact on risperidone response.
