CYP2D6和DRD2基因多态性及其交互作用与阿立哌唑疗效的关联研究

Association of CYP2D6 and DRD2 gene polymorphisms and their interactions with efficacy of aripiprazole in treatment of schizophrenic patients

目的探讨细胞色素P4502D6(CYP2D6)和多巴胺D2受体(DRD2)基因多态性及其交互作用与阿立哌唑治疗精神分裂症临床疗效的关联。方法选取120例接受单一阿立哌唑治疗4周的精神分裂症住院患者为研究对象,采用4周末阳性与阴性症状量表(PANSS)减分率评定药物疗效,其中有效(≥50%)组69例,无效(<50%)组51例。采用多重高温连接酶检测反应技术检测CYP2D6(rs1065852、rs1135840)和DRD2(rs1799732、rs1800497)基因多态性;采用多因子降维法(MDR)分析基因-基因交互作用,多因素logistic逐步回归分析估计CYP2D6和DRD2基因多态性及其交互作用的效应。结果有效组与无效组rs1065852、rs1799732、rs1800497位点等位基因及基因型频率分布比较,差异均有统计学意义(均P<0.05);rs1135840位点等位基因及基因型频率分布比较,差异均无统计学意义(均P>0.05)。rs1065852、rs1799732、rs1800497位点多态性之间存在交互作用。rs1065852、rs1799732、rs1800497多态性及其交互作用均可影响阿立哌唑治疗精神分裂症的疗效,其OR值(95%CI)分别为3.269(1.124~9.510)、0.188(0.048~0.738)、3.314(1.336~8.218)、3.395(1.047~11.001)。结论CYP2D6(rs1065852)和DRD2(rs1799732、rs1800497)基因多态性与阿立哌唑治疗精神分裂症疗效相关,其对阿立哌唑疗效的影响存在正交互作用。

Objective To investigate the association of cytochrome P4502 D6(CYP2 D6)and dopamine D2 receptor(DRD2)gene polymorphisms and their interactions with the clinical efficacy of aripiprazole in the treatment of schizophrenia.Methods A total of 120 schizophrenic patients who treated with aripiprazole alone for 4 weeks were recruited.The score reduction rate of positive and negative symptom scale(PANSS)at the end of 4 weeks of treatment was used to evaluate the efficacy of aripiprazole.There were 69 patients in the effective group(≥50%)and 51 patients in the ineffective group(<50%).The gene polymorphisms of CYP2 D6(rs1065852,rs1135840)and DRD2(rs1799732,rs1800497)were detected by improved multiple ligase detection reaction(i MLDR).Multifactor dimensionality reduction(MDR)was used to analyze gene-gene interactions,and multivariate logistic stepwise regression analysis was used to estimate the effects of CYP2 D6 and DRD2 gene polymorphisms and their interactions.Results There was significant difference in the frequency distribution of alleles and genotypes of rs1065852,rs1799732 and rs1800497 between the effective group and the ineffective group(both P<0.05),while there was no difference in the frequency distribution of alleles and genotypes of rs1135840(both P<0.05).MDR analysis showed that there was an interaction between the gene polymorphisms of rs1065852,rs1799732,and rs1800497.Multivariate logistic stepwise regression analysis showed that the gene polymorphisms of rs1065852,rs1799732,rs1800497 and their interactions affected the clinical efficacy of aripiprazole in the treatment of schizophrenia,and the ORs(95%CI)were 3.269(1.124~9.510),0.188(0.048~0.738),3.314(1.336~8.218)and 3.395(1.047~11.001),respectively.Conclusion The gene polymorphisms of CYP2 D6(rs1065852)and DRD2(rs1799732,rs1800497)are associated with the efficacy of aripiprazole in the treatment of schizophrenia,and their effects on the efficacy of aripiprazole have an positive interaction.