细胞色素P450酶1A2、2D6与多巴胺D2受体基因多态性对奥氮平治疗精神分裂症PANSS减分率的影响  

Influence of Genetic Polymorphisms of Cytochrome P4501A2,2D6 and Dopamine Receptor D2 on the Reduction Rate of PANSS Score of Olanzapine Treatment for Schizophrenia

作　　者：方芳[1] 方海红 宋明芬[3] 闫盼 施剑飞[2] FANG Fang;FANG Haihong;SONG Mingfen;YAN Pan;SHI Jianfei(Hangzhou Seventh People’s Hospital Department of Outpatient,Hangzhou 310013,China;Hangzhou Seventh People’s Hospital Department of Psychiatry,Hangzhou 310013,China;Hangzhou Seventh People’s Hospital Molecular Biological Laboratory,Hangzhou 310013,China)

机构地区：[1]杭州市第七人民医院门诊部,杭州310013 [2]杭州市第七人民医院精神科,杭州310013 [3]杭州市第七人民医院分子生物学实验室,杭州310013

出　　处：《中国现代应用药学》2020年第13期1621-1626,共6页Chinese Journal of Modern Applied Pharmacy

基　　金：浙江省科技厅重大科技专项重大社会发展项目(2015C03054);浙江省医药卫生科技计划项目(2020KY744,2020KY222)。

摘　　要：目的研究细胞色素P450酶(cytochrome P450,CYP)1A2、2D6以及多巴胺D2受体(dopamine receptor D2,DRD2)的基因多态性对奥氮平治疗精神分裂症阳性和阴性症状量表(positive and negative syndrome scale,PANSS)减分率的影响及其程度。方法入组只用奥氮平治疗的精神分裂症住院患者178例,评定治疗前以及治疗4周后的PANSS量表得分,计算减分率。同时,收集血液,测定CYP1A2*1F、CYP2D6*10、DRD2-141C Ins/Del、DRD2-241 A>G、DRD2 Taq1A位点的基因多态性。通过方差分析,比较各基因型PANSS减分率的差异;通过多元线性回归分析,得出减分率的回归方程,并计算决定系数。结果PANSS减分率在CYP1A2*1F(CC:65.68±11.22;CA:55.59±15.40;AA:43.75±15.20)、CYP2D6*10(CC:44.36±16.67;CT:51.78±17.81;TT:56.14±17.13)、DRD2-141C Ins/Del(Ins/Ins:55.11±17.39;Ins/Del:39.16±14.28)和DRD2-241 A>G(AA:45.47±17.52;GA:61.82±10.55;GG:75.43±17.71)不同基因型之间均有统计学显著差异(P均<0.01),而DRD2 Taq1A位点的基因型间PANSS减分率差异无统计学意义。PANSS减分率=58.041-10.703´CYP1A2*1F+4.272´CYP2D6*10-11.921´DRD2-141C Ins/Del+13.443´DRD2-241 A>G(决定系数R2=0.517,P<0.05)。结论CYP1A2*1F、CYP2D6*10、DRD2-141 C Ins/Del、DRD2-241A>G位点基因多态性影响奥氮平治疗精神分裂症疗效,但只解释了减分率的51.7%,有待纳入更多的影响因素进行分析。OBJECTIVE To explore the influence of genetic polymorphisms of cytochrome P450(CYP) 1A2, 2D6 and dopamine receptor D2(DRD2) on the reduction rate of positive and negative syndrome scale(PANSS) score of olanzapine treatment for schizophrenia. METHODS One hundred seventy eight cases of schizophrenia inpatients treated with olanzapine were recruited. PANSS were evaluated at baseline and 4 weeks after olanzapine treatment. The PANSS total score reduction rates were calculated. Meanwhile, their blood was collected for genetic polymorphism detections of CYP1A2*1F, CYP2 D6*10, DRD2-141C Ins/Del, DRD2-241 A>G and DRD2 Taq1A. The difference of PANSS score reduction rates among genotypes in each gene were compared by analysis of variance, and its regression equation was obtained by multivariate linear regression analysis. RESULTS The PANSS reduction rates among genotypes in CYP1A2*1F(CC: 65.68±11.22, CA: 55.59±15.40, AA: 43.75±15.20), CYP2D6*10(CC: 44.36±16.67;CT: 51.78±17.81;TT: 56.14±17.13), DRD2-141 C Ins/Del(Ins/Ins: 55.11±17.39, Ins/Del: 39.16±14.28) and DRD2-241 A>G(AA: 45.47±17.52;GA: 61.82±10.55;GG: 75.43±17.71) were obviously different(all P<0.01). However, the reduction rates in DRD2 Taq1A genotypes did not show a significant change(P>0.05). PANSS reduction rate=58.041-10.703′CYP1A2*1F+4.272′CYP2D6*10-11.921′DRD2-141C Ins/Del+13.443′DRD2-241A>G(R^2=0.517, P<0.05). CONCLUSION Genetic polymorphisms of CYP1A2*1F, CYP2D6*10, DRD2-141C Ins/Del, and DRD2-241A>G can influence efficacy of olanzapine treatment for schizophrenia patients, but they only accounted for 51.7% of the reduction. More influencing factors are needed to be included for analysis.

关 键 词：细胞色素P450酶 多巴胺D2受体 基因多态性 奥氮平 精神分裂症 

分 类 号：R969.3[医药卫生—药理学]