【摘要】 目的:探讨中国人群中氯氮平所致粒细胞减少症与HSP70-2 mRNA表达及HSP70-2基因多态的关系。方法:将符合精神分裂症诊断标准的广州医学院附属精神病医院住院或门诊患者,根据单一使用氯氮平后外周血白细胞及中性粒细胞绝对计数分为氯氮平所致粒细胞减少症组(简称减少组)、服用氯氮平粒细胞正常组(简称正常组)及氯氮平所致粒细胞增多组(简称增多组)。三组精神分裂症研究组均于抽血做检测时同时抽血做氯氮平血药浓度检查,采用自行设计的调查表收集临床病史及人口学资料。采用聚合酶链反应-限制性长度片段多态性(PCR-RFLP)分析HSP70-2 G1267A多态,采用实时荧光定量PCR(QPCR)检测三组患者的HSP70-2 mRNA表达。结果:减少组、正常组与增多组间氯氮平使用剂量、血药浓度无显著性差异(P>0.05);三组中性粒细胞的HSP70-2 mRNA表达水平有统计学显著性差异(P<0.01),粒细胞增多组患者中性粒细胞的HSP70-2 mRNA表达增强;HSP70-2基因1267位点各基因型及等位基因频率在三组人群的分布无显著性差异(P>0.05);HSP70-2 G1267A三种基因型的HSP70-2 mRNA表达水平无显著性差异(P>0.05)。结论:氯氮平所致的粒细胞减少症与氯氮平使用剂量及血药浓度关无;氯氮平所致的粒细胞增多患者中性粒细胞的HSP70-2 mRNA表达增强,可能由于HSP70蛋白独特的抗凋亡保护作用及其使用氯氮平后表达的增强,造成了使用氯氮平后出现的粒细胞增多现象;氯氮平所致的粒细胞减少症与HSP70-2mRNA表达无关;中国人群中的氯氮平所致的粒细胞减少症可能与HSP70-2 G1267A多态无关;HSP70-2 G1267A突变对中性粒细胞中HSP70-2 mRNA表达影响不大。更多还原

【Abstract】 Objective:To study the characteristics of HSP70-2 mRNA expression and HSP70-2 gene polymorphism in Chinese population in patients with clozapine induced granulocytopenia.in the Han Chinese.Methods:Patients and outpatients from Psychiatric Hospital of Guangzhou Medical College affiliated hospital that meet the third edition classification and diagnostic criteria for mental disorders(CCMD-3) for schizophrenia were divided into three groups according to peripheral blood leukocytes and neutral granulocyte counts after a single use of clozapine: clozapine induced granulocytopenia group(reduction group),granulocyte normal group(normal group) and clozapine induced granulocyte increased group(increase group).The blood plasma concentration of clozapine was detected when blood test done by all patients from three groups,and the clinical history and demographic information was collected using own-designed questionnaire.the expression of HSP70-2 mRNA was detected through Real-time fluorescence quantitative PCR(QPCR).The HSP70-2-G1267A polymorphism was analysised by Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Results: There was no significant differences(P>0.05) among three groups in Clozapine dose and plasma concentration;There were statistically significant differences(P<0.01) in HSP70-2 mRNA expression levels of neutrophil from three groups;The expression of HSP70-2 mRNA in neutrophils has increased specially in increase group.There was no significant differences(P>0.05)in the distribution of genotypes and allele frequency of HSP70-2 gene at 1267 points of three groups.The HSP70-2 mRNA expression levels of three genotypes of HSP70-2-G1267A were not significantly different(P>0.05).Conclusions: Clozapine-induced granulocytopenia was not related with clozapine dose and plasma concentration;The expression of HSP70-2 mRNA in neutrophils has increased specially in increase group;The increased granulocyte after usage of clozapine may caused by the unique anti-apoptosis of HSP70-2 protein and its increased expression after the use of clozapine.The Clozapine-induced granulocytopenia has no correlation with the expression decrease of HSP70-2 mRNA.Clozapine-induced granulocytopenia in Chinese population might have nothing to do with polymorphism of HSP70-2-G1267A.The mutation of HSP70-2 G1267A had little effect on expression levels of HSP70-2 mRNA in neutrophils.更多还原