人类白细胞抗原基因多态性与服用氯氮平患者白细胞计数相关性研究  

Correlation Between Human Leucocyte Antigen Gene Polymorphism and Leukocyte Count in Patients Treated with Clozapine

作　　者：王姝姗 曲衎衎 朱浩浩 张忠东 WANG Shushan;QU Kankan;ZHU Haohao;ZHANG Zhongdong(Department of Pharmacy,The Affiliated Wuxi Mental Health Center of Nanjing Medical University,Wuxi,Jiangsu,China 214151)

机构地区：[1]南京医科大学附属无锡精神卫生中心药学部,江苏无锡214151

出　　处：《中国药业》2021年第16期68-70,共3页China Pharmaceuticals

基　　金：江苏省无锡市卫生计生科研面上项目[MS201716]。

摘　　要：目的探讨人类白细胞抗原基因(HLA-B*57∶01、HLA-B*35∶08)多态性与服用氯氮平精神分裂症患者外周血白细胞计数(WBC)的相关性。方法选取医院2018年至2019年收治的服用氯氮平的精神分裂症住院患者150例。采用多重SNaPShot方法检测患者的基因类型,采用全自动二维液相色谱仪分析患者的氯氮平血药浓度,比较不同基因型患者的氯氮平血药浓度及WBC。结果女性患者的氯氮平血药浓度明显高于男性(P<0.05);不同日剂量患者的氯氮平血药物浓度-剂量比及2种基因各基因型间氯氮平血药浓度无显著差异(P>0.05);HLA-B*35∶08基因中突变(A/A)型WBC明显低于杂合(G/A)型和野生(G/G)型(P<0.05),HLAB*57∶01各基因型间WBC无显著差异(P>0.05)。结论HLA-B*35∶08基因类型与患者的WBC相关,提示WBC减少的HLA基因的免疫源性因素,该结论可为临床安全使用氯氮平提供参考。Objective To investigate the correlation between human leukocyte antigen gene(HLA-B*57∶01,HLA-B*35∶08)polymorphism and peripheral blood white blood cell count(WBC)in schizophrenic patients treated with clozapine.Methods A total of 150 schizophrenic inpatients treated with clozapine in our hospital from 2018 to 2019 were selected.Multiple SNaPShot method was used to detect the patients genotypes.The plasma concentration of clozapine was analyzed by automatic two-dimensional liquid chromatogra-phy,and the plasma concentration of clozapine and WBC of patients with different genotypes were compared.Results The plasma concentration of clozapine in female patients was significantly higher than that in male patients(P<0.05).There was no significant difference in plasma dose-concentration ratio of clozapine among patients with different daily dose,and there was no significant difference in plasma concentration of clozapine between the two genotypes(P>0.05).The WBC of patients with mutation(A/A)of HLA-B*35∶08 gene was significantly lower than that of heterozygous(G/A)type and wild(G/G)type of HLA-B*35∶08 gene(P<0.05).There was no significant difference in WBC of patients with different HLA-B*57∶01 genotypes(P>0.05).Conclusion HLA-B*35∶08 genotype is related to patients’WBC,which suggests that the HLA gene is an immunogenic factor of leukopenia,and it can provide a reference for the safe use of clozapine in the clinic.

关 键 词：氯氮平 血药浓度 白细胞减少症 HLA-B*57∶01基因 HLA-B*35∶08基因 基因多态性 相关性 

分 类 号：R969.2[医药卫生—药理学]