细胞色素P4502D6及多巴胺D2受体基因多态性与利培酮疗效的关联

摘要

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 D2 receptor,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/C 188T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/C 188T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 DRD2TaqIA between the case group and the control group(AlAl:29.1% vs. 35.9%,A1A2:37.7% vs. 47.5%, A2A2:33.2% vs. 16.6%, P ＜ 0.05; Al:48.0% vs. 59.6%, A2:52.0% vs. 40.4%, P ＜0.05). The association of the interaction of CYP2D6/C188T and DRD2TaqIA with the reducing rates of PANSS(F = 0.735, P ＞ 0.05) was not significant. However, the association became significant after adjustment for sex (F = 3.214, P ＜ 0.05). Conclusions The polymorphisms of CYP2D6 gene C/T188 and DRD2 gene TaqlA are not genetic susceptibility factors for therapeutic response to risperidone in subjects with schizophrenia. When covariate is sex, the interaction of CYP2D6/C188T and DRD2TaqIA is a susceptibility factor for the treatment response to risperidone.