作　　者： ; ; ;

机构地区： 广东省妇幼保健院

出　　处： 《中国临床药理学杂志》 2019年第11期1128-1131,共4页

摘　　要： 目的探讨多巴胺D1受体(DRD1) rs5326、rs4532和rs265981基因多态性对氯氮平片治疗精神分裂症疗效的影响。方法 54例精神分裂症患者均给予氯氮平每次150 mg,qd,口服,治疗8周。用高效液相色谱法测定氯氮平的稳态谷浓度,用阳性与阴性症状量表(PANSS)评定临床疗效,用限制性片段长度多态性聚合酶链反应技术检测DRD1 rs5326、rs4532和rs265981基因多态性,并进行关联分析。结果治疗后,所有患者的平均氯氮平血药浓度为(246. 76±28. 84)ng·mL-1,DRD1 rs5326、rs4532和rs265981各基因型患者体内氯氮平血液浓度与总体平均血药浓度比较,差异均无统计学意义(均P> 0. 05)。治疗后,DRD1rs5326 GG基因型的总疗效与阳性症状疗效分别为93. 75%和87. 50%,均明显高于DRD1 rs5326 GA/AA的68. 42%/33. 33%和66. 16%/33. 33%,差异均有统计学意义(均P <0. 05);DRD1 rs265981 CC基因型的总疗效与阳性症状疗效分别为93. 94%和87. 88%,均明显高于DRD1 rs265981 TT/TC的73. 33%/66. 67%和60. 00%/50. 00%,差异均有统计学意义(均P <0. 05);DRD1 rs4532AA基因型的阴性症状疗效为78. 95%,均明显高于DRD1 rs4532 AG/GG的50. 00%和0,差异均有统计学意义(均P <0. 05)。结论氯氮平治疗精神分裂症的总疗效及阳性症状疗效可能与DRD1 rs5326和rs265981多态性有关,阴性症状疗效可能与DRD1 rs4532有关。 Objective To investigate the effects of dopamine D1 receptor(DRD1)rs5326,rs4532 and rs265981 gene polymorphisms on the efficacy of clozapine tablets in the treatment of schizophrenia.Methods A total of 54 patients with schizophrenia were treated with clozapine150 mg per,qd,orally for 8 weeks.The stable trough concentration of clozapine was determined by high performance liquid chromatography.The clinical efficacy was evaluated by the positive and negative symptoms scale(PANSS).The DRD1 rs5326,rs4532 and rs265981 gene polymorphisms were detected by restriction fragment length polymorphism polymerase chain reaction,and correlation analysis was caculated.Results After treatment,the mean blood concentration of clozapine in all patients was(246.76±28.84)ng·mL-1.There were no significant differences on the clozapine blood concentration in patients with DRD1 rs5326,rs4532 and rs265981 genotypes compared with the overall mean blood concentration(all P>0.05).After treatment,the total efficacy and positive symptoms efficacy of DRD1 rs5326 GG genotype were 93.75%and 87.50%,which were significantly higher than those of DRD1 rs5326 GA/AA(68.42%/33.33%and 66.16%/33.33%,all P<0.05).The total efficacy and positive symptoms efficacy of DRD1 rs265981 CC genotype were 93.94%and 87.88%,which were significantly higher than those of DRD1 rs265981 TT/TC(73.33%/66.67%and 60.00%/50.00%,all P<0.05).The negative symptoms of DRD1 rs4532 AA genotype were78.95%,which were significantly higher than those of DRD1 rs4532 AG/GG(50.00%and 0%,all P<0.05).Conclusion The total efficacy and positive symptoms of clozapine in the treatment of schizophrenia may be related to the polymorphism of DRD1 rs5326 and rs265981,and the efficacy of negative symptoms may be related to DRD1 rs4532.

关 键 词： 氯氮平片 精神分裂症 多巴胺 受体 基因多态性

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