摘要
目的系统评价中国人群中基因多态性与氯丙嗪的药效学和药物不良反应的相关性。方法检索Pub Med、EMbase、Web of Science、The Cochrane Library、中国知网、万方数据库和维普数据库,检索时间均从建库至2018-09-18。收集有关基因多态性对氯丙嗪药效学和药物不良反应影响的研究,对纳入研究的药效学及药物不良反应指标进行系统评价。结果共纳入9项研究。DRD1基因rs686位点等位基因A、G的分布对于氯丙嗪改善阳性症状的差异有统计学意义(x^2=3. 939,P <0. 05),rs686等位基因A是氯丙嗪改善阳性症状疗效较好的预测因子;携带DRD2基因-141CIns/Del位点等位基因Del的患者相比于无此等位基因的患者具有更显著的简明精神病量表减分率; 5-HTR2A基因rs6311等位基因A、G的分布在氯丙嗪有效组与无效组之间差异有统计学意义(x^2=3. 939,P <0. 05),等位基因A的携带者对氯丙嗪总疗效优于等位基因G的携带者; BDNF基因(GT) n 230-bp与234-bp等位基因的频率对于患者服用氯丙嗪后是否发生锥体外系反应的差异有统计学意义(230-bp:P <0. 01,OR=0. 398,95%CI=0. 213～0. 745; 234-bp:P <0. 01,OR=2. 256,95%CI=1. 289～3. 947)。携带230-bp等位基因的患者服药后不易产生椎体外系反应,而携带234-bp等位基因的患者服药后易产生椎体外系反应。SLC6A3 (rs2975226)、CYP2C19(rs4986893)基因多态性对氯丙嗪药效学及药物不良反应的影响尚无明确定论。结论 DRD1(rs686)、DRD2(-141C Ins/Del)、5-HTR2A(rs6311)与BDNF(GT) n基因多态性可能影响氯丙嗪药效学和药物不良反应,在临床使用氯丙嗪时应充分考虑到我国人群基因多态性,保证药物使用的有效与安全性。
Objective Systematically reviewing the associations between the gene polymorphism and the pharmacodynamics and adverse reaction of chlorpromazine in chinese population.Methods PubMed,EMbase,Web of Science,The Cochrane Library,CNKI,WanFang Data and WeiPu Data were searched from database establish time to September18 th,2018.Collecting literature on the impact of gene polymorphism on the pharmacodynamics and adverse reactions of chlorpromazine,and systematically reviewing the indicator of the pharmacodynamics and adverse reactions in the enrolled literature.Results Totally 9 studies were included.The distribution of DRD1 gene rs686 allele A/G had statistically significant differences to chlorpromazine improving the positive symptom(x^2=3.939,P<0.05),rs686 allele A is the predictors of better therapeutic response to chlorpromazine in positive symptom;the patients with Del allele in DRD2 gene-141 C Ins/Del have a significantly decreased BPRS score compared to those with no Del allele;the distribution of 5-HTR2 A gene rs6311 allele A/G had statistically significant differences between the the responsers and non-responsers(x^2=3.939,P<0.05),5-HTR2 A gene rs6311 allele A is associated with increased response to chlorpromazine in people with schizophrenia as compared to allele G.The frequencies of BDNF gene(GT)n 230-bp allele and 234-bp allele showed significant differences between patients with chlorpromazine-induced extrapyramidal system reaction(EPS)and those without chlorpromazine-induced EPS(230-bp:P<0.01,OR=0.398,95%CI=0.213-0.745;234-bp:P<0.01,OR=2.256,95%CI=1.289-3.947),and the patients with the 230-bp allele of the(GT)n polymorphism in BDNF gene exhibited a lower degree of induced extrapyramidal syndrome,while those with 234-bp less susceptible to chlorpromazine-induced EPS.And the associations between the SLC6 A3 gene rs2975226,CYP2 C19 gene rs4986893 polymorphisms and vivo pharmacodynamics/adverse drug reaction of chlorpromazine are not clearly concluded.Conclusions DRD1 rs686,DRD2-141 C Ins/Del,5-HTR2 A rs631
作者
吴松涛
张晓丹
周双
赵侠
周颖
崔一民
WU Song-tao;ZHANG Xiao-dan;ZHOU Shuang;ZHAO Xia;ZHOU Ying;CUI Yi-min(Department of Pharmacy,Peking University First Hospital,Beijing 100034,China;Department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical Science,Peking University,Beijing 100191,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2019年第3期294-297,共4页
The Chinese Journal of Clinical Pharmacology
基金
国家科技重大专项--重大新药创制资助项目(2017ZX09101001)
关键词
氯丙嗪
基因多态性
中国人群
药效学
药物不良反应
chlorpromazine
gene polymorphism
Chinese
pharmacodynamics
adverse drug reaction
