摘要
目的探讨细胞色素P450(CYP)3A5×3(rs776746)基因多态性对肾移植受者他克莫司(FK506)代谢的影响。方法选取2016年1月—2017年12月于我院行肾移植术,术后接受以他克莫司为基础的三联抗排斥方案(他克莫司+霉酚酸酯+激素)治疗且术后定期门诊随访的190例肾移植受者的临床资料,收集其2年内的随访信息。采用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)检测CYP3A5基因多态性,根据CYP3A5基因型分为CYP3A5×1/×1组,CYP3A5×1/×3组,CYP3A5×3/×3组,记录3组受者术后不同时间点(7天、1个月、3个月、6个月、1年和2年)有效的血他克莫司浓度/剂量(C0/D)值,术后急性排斥反应和感染发生情况,血药浓度检测采用酶联免疫放大法。结果190例肾移植受者中,CYP3A5×1/×1组,CYP3A5×1/×3组,CYP3A5×3/×3组的例数分别为:24例、66例、100例。术后不同随访时间点CYP3A5×3/×3组受者的C0/D值均明显高于CYP3A5×1/×1组和CYP3A5×1/×3组(P<0.05),CYP3A5×1/×1组和CYP3A5×1/×3组患者各时间点C_0/D值无统计学差异(P>0.05)。术后2年内CYP3A5×1/×1组急性排斥反应发生率高于CYP3A5×1/×3组和CYP3A5×3/×3组(P=0.032,P<0.001),而术后2年内CYP3A5×1/×3组和CYP3A5×1/×3组急性排斥反应发生率无统计学差异(P=0.28)。术后2年内各组感染发生率无统计学差异(P>0.05)。结论CYP3A5基因多态性对肾移植术后受者他克莫司代谢有明显影响,结合CYP3A5基因分型有利于个体化用药。
Objective To investigate the influence of CYP3 A5 genetic polymorphisms on tacrolimus pharmacogenetics in renal transplant recipients.Methods 190 renal transplant recipients treated with tacrolimus in our hospital were genotyped for CYP3 A5(6986 A>G)single nucleotide polymorphisms,and were followed up regularly in outpatient department.According to the CYP3 A5 genotype,the patients were divided into CYP3 A5×1/×1 group,CYP3 A5×1/×3 group and CYP3 A5×3/×3 group.The effective blood tacrolimus concentration/dose(C0/D)value,acute rejection and infection were recorded at different time points(7 days,1 month,3 months,6 months,1 year and 2 years).Genotypes were correlated to tacrolimus daily dose and concentration/dose ratio post-transplantation and with incidence of acute rejection and infection.Enzyme linked immunosorbent assay was used to monitor the drug concentration.Results Among 190 renal transplant recipients,the number of cases in CYP3 A5×1/×1 group,CYP3 A5×1/×3 group and CYP3 A5×3/×3 group were 24 cases,66 cases and 100 cases,respectively.The C0/D values of patients in CYP3 A5×3/×3 group were significantly higher than those in CYP3 A5×1/×1 and CYP3 A5×1/×3 groups at different follow-up time points(P<0.05).The incidence of rejection in CYP3 A5×1/×1 group was higher than that in CYP3 A5×1/×3 group and CYP3 A5×3/×3 group within 2 years after transplantation(P=0.032,P<0.001),but there was no significant difference in the incidence of rejection between CYP3 A5×1/×3 group and CYP3 A5×1/×3 group(P=0.28).There was no significant difference in the incidence of infection among the groups within 2 years after transplantation(P>0.05).Conclusion CYP3 A5 genetic polymorphism is associated with concentration/dose ratio.Screening for this polymorphism could be helpful to choose the suitable calcineurin inhibitors or determine the suitable initial dose.
作者
张异蕊
郭予和
陈正
ZHANG Yirui;GUO Yuhe;CHEN Zheng(Organ Transplant Center,the 2^(nd) Affiliated Hospital of Guangzhou Medical University,Guangzhou 510260,China;不详)
出处
《现代医院》
2021年第4期642-645,共4页
Modern Hospitals
基金
广东省临床用药基金(2020ZJ03)
广东省科技计划项目(2015B020226002)。
