细胞色素P450 2D6及多巴胺D2受体基因多态性与利培酮疗效的关联

An association study of the cytochromes P4502D6,the dopamine D2 receptor gene polymorphisms and efficacy of risperidone

目的探讨细胞色素P450 2D6(cytochromes P450 2D6,CYP2D6)基因多态性、多巴胺D2受体(dopamine D2receptor,DRD2)基因多态性与利培酮疗效的相关性。方法对199例首发精神分裂症患者给予利培酮治疗8周,治疗前后采用阳性和阴性症状量表(Positive and Negative Syndrome Scale,PANSS)评定疗效,同时收集198例正常对照进行病例-对照分析。采用聚合酶链反应序列特异性引物扩增技术检测CYP2D6/C188T、DRD2 TaqIA基因型,分析二者与利培酮临床效应的相关性。结果病例组和对照组CYP2D6/C188T的基因型和等位基因频率相比,差异有统计学意义(CC:40.7%vs.21.2%,CT:25.6%vs.45.5%,TT:33.7%vs.33.3%,P<0.05;C:53.5%vs.43.9%,T:46.5%vs.56.1%,P<0.05),病例组和对照组DRD2 TaqIA的基因型和等位基因频率相比,差异有统计学意义(A1A1:29.1%vs.35.9%,A1A2:37.7%vs.47.5%,A2A2:33.2%vs.16.6%,P<0.05;A1:48.0%vs.59.6%,A2:52.0%vs.40.4%,P<0.05);CYP2D6/C188T与DRD2TaqIA的交互作用对PANSS减分率的影响没有统计学意义(F=0.735,P>0.05);CYP2D6/C188T,DRD2TaqIA与性别的交互作用对PANSS减分率的影响具有统计学意义(F=3.214,P<0.05)。结论 CYP2D6基因C188T多态性和DRD2基因TaqIA多态性不是影响精神分裂症患者利培酮临床疗效的易感因素,但是在协变量性别的作用下,上述基因多态性的交互作用可能影响利培酮的疗效。

Objective To investigate the correlation of polymorphisms of cytochromes P450 2D6, dopamine D2 receptor and efficacy of risperidone treatment. Methods One hundred ninety-nine first episode schizophrenics were treated with Risperidone for 8 weeks and 198 healthy people served as controls. Positive and Negative Syndrome Scale was used to evaulate the efficacy of risperidone. PCR-RFLP was used to detect the polymorphisms of the CYP2D6 C/T188and DRD2TaqIA genotypes. Results There were significant differences in the ratio of genotypes, al- lele frequency of CYP2D6/C188T between the case group and the control group（CC：40.7% vs. 21.2%, CT：25.6% vs. 45.5%, TT： 33.7% vs. 33.3%, P 〈 0.05; C：53.5% vs. 43.9%, T：46.5% vs. 56.1%, P 〈 0.05）. There were significant differences in the ratio of genotypes, allele frequency of DRD2TaqlA between the case group and the con- trolgroup（A1Al：29.1% vs. 35.9%,A1A2：37.7% vs. 47.5%, A2A2：33.2% vs. 16.6%, P〈 0.05; A1：48.0% vs. 59.6%, A2：52.0% vs. 40.4%, P 〈 0.05）. The association of the interaction of CYP2D6/C188T and DRD2TaqlA with the reducing rates of PANSS（F = 0.735, P 〉 0.05） was not significant. However, the association became signif- icant after adjustment for sex （F = 3.214, P 〈 0.05）. Conclusions The polymorphisms of CYP2D6 gene C/T188 and DRD2 gene TaqIA are not genetic susceptibility factors for therapeutic response to risperidone in subjects with schizophrenia. When covariate is sex, the interaction of CYP2D6/C188T and DRD2TaqlA is a susceptibility factor for the treatment response to risperidone.