环磷酰胺代谢酶基因多态性与膜性肾病的相关性研究  

Correlation between cyclophosphamide metabolic enzyme gene polymorphism and membranous nephropathy

作　　者：陈燕红 侯幸赟 喻勇嘉 陆馨怡 高颖 张凤 CHEN Yanhong;HOU Xingyun;YU Yongjia;LU Xinyi;GAO Ying;ZHANG Feng(Department of Pharmacy,Shanghai Changzheng Hospital,Naval Medical University(Second Military Medical University),Shanghai 200003,China)

机构地区：[1]海军军医大学第二附属医院(上海长征医院)药剂科,上海200003

出　　处：《世界临床药物》2023年第5期493-498,共6页World Clinical Drug

基　　金：上海市卫生健康委员会青年课题(20194Y0035);上海市“医苑新星”青年医学人才培养资助计划(青年医学人才类——临床药师项目)。

摘　　要：目的探讨环磷酰胺(cyclophosphamide,CTX)代谢酶基因多态性和膜性肾病(membranous nephropathy,MN)的相关性,为个体化给药提供依据。方法分析2021年1月至2022年10月在上海长征医院肾内科就诊的80例使用CTX的MN患者的临床资料,检测CTX代谢酶基因(CYP2C19^(*)2、CYP2C19^(*)3、CYP3A5、GSTP1),观察并分析患者在使用CTX时及治疗后第1、3、6及12个月的24 h尿蛋白定量、血清白蛋白及肌酐(creatinine,Cr)等指标变化及药物不良事件发生情况。结果CYP2C19^(*)2、CYP2C19^(*)3、CYP3A5、GSTP1频率分布符合Hardy-Weinberg平衡分布。CYP2C19^(*)2 GA基因型携带者,24 h尿蛋白定量、血清白蛋白、Cr水平较治疗前差异具有统计学意义(P<0.05);CYP2C19^(*)3 GG、GA、AA基因型携带者,24 h尿蛋白定量、血清白蛋白、Cr水平较治疗前差异无统计学意义(P>0.05);CYP3A5 AG基因型携带者,Cr水平较治疗前差异具有统计学意义(P<0.05),但对血清白蛋白及24 h尿蛋白定量无明显影响;GSTP1 AA、AG、GG基因型携带者,24 h尿蛋白定量、血清白蛋白、Cr水平较治疗前差异无统计学意义(P>0.05)。结论CTX代谢酶CYP2C19^(*)2基因多态性对MN的疗效可能存在显著影响,对GA基因型携带者疗效更好,CYP3A5 AG基因型携带者的Cr水平显著降低。Objective To investigate the correlation between gene polymorphism of cyclophosphamide(CTX)metabolic enzyme and membranous nephropathy(MN),and to provide a basis for individualized drug administration.Methods The clinical data of 80 MN patients treated with CTX in the department of nephropathy,Shanghai Changzheng hospital from January 2021 to October 2022 were analyzed,and the metabolic enzyme genes of CTX(CYP2C19^(*)2,CYP2C19^(*)3,CYP3A5,GSTP1)were detected.The changes of 24 h urinary protein quantity,serum albumin,creatinine(Cr)and the adverse drug events were observed and analyzed when CTX was used and 1,3,6,and 12 months after treatment.Results The frequency distributions of CYP2C19^(*)2,CYP2C19^(*)3,CYP3A5 and GSTP1 were consistent with Hardy-Weinberg equilibrium distribution.In CYP2C19^(*)2 GA genotype carriers,there were significant difference in 24 h urinary protein,serum albumin and Cr levels compared with those before treatment(P<0.05).In CYP2C19^(*)3 GG,GA and AA genotype carriers,there was no significant difference in 24 h urinary protein,serum albumin and Cr levels compared with those before treatment(P>0.05).In CYP3A5 AG genotype carriers,there was a significant difference in Cr level compared with that before treatment(P<0.05),but there was no significant difference in serum albumin and 24 h urinary protein quantification.In glutathione S-transferase pi-1 AA,AG and GG genotype carriers,there was no significant difference in 24 h urinary protein,serum albumin and Cr levels compared with those before treatment(P>0.05).Conclusion The gene polymorphism of CTX metabolic enzyme CYP2C19^(*)2 may have a significant effect on the efficacy of MN,and the efficacy of GA genotype carriers is better.The Cr level in CYP3A5 AG genotype carriers is significantly reduced.

关 键 词：环磷酰胺代谢酶 基因多态性 膜性肾病 

分 类 号：R966[医药卫生—药理学] R692[医药卫生—药学]