CYP3A5基因多态性对心脏移植患者体内他克莫司代谢影响的meta分析

Effect of CYP3A5 gene polymorphism on tacrolimus metabolism of heart transplantation patients:a meta-analysis

目的系统评价CYP3A5基因多态性与心脏移植患者术后他克莫司(tarcolimus,FK506)剂量校正浓度(C/D)的相关性。方法通过检索PubMed、Cochrane Library、Embase、Epub Ahead of Print、CNKI、万方、维普数据库,检索时限为建库—2022年11月。采用Rev Man5.3软件进行统计分析。结果共纳入7项研究,包含422例患者。结果显示,心脏移植患者术后CYP3A5*3/*3携带者FK506血药浓度显著高于CYP3A5*1/*3或CYP3A5*1/*1型携带者(P<0.00001)。种族亚组分析结果显示,术后1、6、12个月时,白种人组、亚洲人组与其他种族组中CYP3A5*3/*3携带者血药浓度显著增高。对于年龄的亚组分析结果显示,携带CYP3A5*3/*3基因型成年患者FK506血药浓度较高,而儿童患者CYP3A5基因多态性与FK506体内代谢无显著相关性。结论心脏移植术后患者体内FK506血药浓度与CYP3A5基因型显著相关,CYP3A5*1/*1或CYP3A5*1/*3型心脏移植患者服用FK506的剂量需适当增加,才能达到有效的抗免疫排斥反应治疗效果。

Objective To research the correlation between CYP3A5 gene polymorphism and dose-releted concentration(C/D)of postoperative tacrolimus(FK506)of heart transplantation patients.Methods The databases of PubMed,Cochrane Library,Embase,Epub Ahead of Print,China National Knowledge Infrastructure(CNKI),WanFang Data Knowledge Service Platform(WanFang),Vip Chinese Science and Technology Journal Database(VIP)from database construction to November 2022 were searched and analyzed.All statistical analyses were performed with Rev Man 5.3 software.Results 7 researches with a total of 422 patients were finally included.The results showed that FK506 concentration was significantly higher in CYP3A5*3/*3 phenotype carriers than that in CYP3A5*1/*3 or CYP3A5*1/*1 phenotype carriers after heart transplantation(P<0.00001).Additionally,the ethnic subgroup results showed that in the 1st,6th and 12th months after operation,CYP3A5*3/*3 phenotype significantly increased FK506 concentration in Caucasian,Asian and other ethnic subgroups.As for age subgroup analysis,higher concentrations of tacrolimus were found in adult patients with CYP3A5*3/*3 phenotype,while in children,the CYP3A5 gene polymorphism did not significantly affect the tacrolimus metabolism.Conclusion The present meta-analysis demonstrated that CYP3A5 genes could significantly affect FK506 concentration in heart transplantation patients,among whom CYP3A5*1/*1or CYP3A5*1/*3 gene carriers might need appropriately higher doses of tacrolimus to produce anti-rejection effect.