原发性肾病综合征患儿CYP3A4、CYP3A5、POR和ABCB1基因多态性与他克莫司血药浓度及不良反应的关系  

Association of CYP3A4,CYP3A5,POR and ABCB1 Gene Polymorphisms with Tacrolimus Plasma Concentration and Adverse Reactions in Children with Primary Nephrotic Syndrome

作　　者：黄婉虹 陈秋林 Huang Wanhong;Chen Qiulin(Pharmacy Department,The First Affiliated Hospital of Xiamen University,Xiamen,Fujian,361003,China)

机构地区：[1]厦门大学附属第一医院药剂科,福建厦门361003

出　　处：《黑龙江医学》2024年第17期2051-2053,2057,共4页Heilongjiang Medical Journal

基　　金：福建中医药大学校管课题项目(XB2020159)。

摘　　要：目的:探讨原发性肾病综合征患儿细胞色素P4503A4酶(CYP3A4)、细胞色素P4503A5酶(CYP3A5)、细胞色素P450氧化还原酶(POR)和多药耐药性蛋白1(ABCB1)基因多态性与他克莫司血药浓度及不良反应的相关性。方法:选取于2018年10月—2019年10月厦门大学附属第一医院诊断为原发性肾病综合征并且服用他克莫司的120例患儿作为研究对象,检测其CYP3A4(rs2242480)、CYP3A5(rs776746)、POR(rs1057868)和ABCB1(rs1128503)基因型,并收集病例资料进行回顾性分析。结果:纳入分析的原发性肾病综合征患儿共120例,在CYP3A5中AA基因型(非表达型)患儿血药浓度比GG和GA基因型(表达型)显著升高,差异有统计学意义(t=-9.225,P<0.001)。在CYP3A5表达和非表达型中,CYP3A4、POR和ABCB1不同基因型均与他克莫司血药浓度无关,差异无统计学意义(P>0.05)。CYP3A5非表达基因型患儿使用他克莫司后肝损伤和肾损伤不良反应明显高于表达基因型患儿,差异有统计学意义(P<0.05)。logistics回归分析结果显示,与CYP3A5非表达基因型比较,表达基因型患儿肝损伤和肾损伤风险分别降低了0.31倍和0.32倍。CYP3A4、PRO和ABCB1不同基因型与患儿消化道反应、血糖异常升高、肝损伤和肾损伤发生率无关,差异无统计学意义(P>0.05)。结论:原发性肾病综合征患儿CYP3A5基因多态性与他克莫司血药浓度具有相关性,非表达基因型会增加肝损伤和肾损伤的风险。Objective:To explore the relationship between CYP3A4,CYP3A5,POR and ABCB1 gene polymorphisms,tacrolimus plasma concentration and adverse reactions in children with primary nephrotic syndrome.Methods:Collecting 120 children diagnosed with primary nephrotic syndrome and taking tacrolimus in the hospital from October 2018 to October 2019,testing their CYP3A4(rs2242480),CYP3A5(rs776746),POR(rs1057868)and ABCB1(rs1128503)genotypes,and conducting clinical data for analysis.Results:A total of 120 children with primary nephrotic syndrome were included in the analysis,the plasma concentration of children with CYP3A5 AA genotype(non expression group)was higher than that of GG and GA genotypes(expression group),and the difference was statistically significant(t=-9.225,P<0.001).In the CYP3A5 of expression and non expression groups,the different genotypes of CYP3A4,POR and ABCB1 were not related to the plasma concentration of tacrolimus,and the difference was not statistically significant(P>0.05).The adverse drug reactions of liver injury and kidney injury in children with CYP3A5 non expression group were significantly higher than expression group(P<0.05).The results of logistic regression analysis showed that compared with the non expression group of CYP3A5,the risk of liver injury and kidney injury in children with the expression group was reduced by 0.31 and 0.32 times.The different genotypes of CYP3A4,PRO,and ABCB1 were not associated with related adverse reaction,and the differences were not statistically significant(P>0.05).Conclusion:CYP3A5 gene polymorphism is associated with tacrolimus plasma concentration in children with primary nephrotic syndrome,and non expression genes will increase the risk of liver and kidney injury.

关 键 词：他克莫司 基因多态性 原发性肾病综合征 不良反应 

分 类 号：R692[医药卫生—泌尿科学]