摘要
目的探究细胞色素酶CYP3A5(rs776746)基因多态性对稳定期肝移植受者他克莫司(TAC)药物浓度和肝肾功能的影响。方法选择2015年3月—2020年6月于本院行肝移植术并接受以TAC为基础的抗排斥方案治疗且定期门诊随访的稳定期肝移植受者132例,采用目的片段PCR扩增和直接测序法检测CYP3A5基因型;采用电化学发光磁微粒免疫分析法检测肝移植受者的TAC药物谷浓度,计算经体质量和日剂量校正的标准化血药浓度(C/D)值;采用酶法或速率法检测肝移植受者肝肾功能指标。结果132例肝移植受者中,CYP3A5*1/*1型(AA)、*1/*3型(AG)、*3/*3型(GG)的例数(频率)分别为9例(9.85%)、51例(38.64%)和68例(51.51%)。等位基因*1(A)和*3(G)的频率分别为29.17%和70.83%,各基因型频率符合Hardy-Weinberg遗传平衡(χ^(2)=3.67,P>0.05)。不同基因型受者TAC药物谷浓度差异无统计学意义(P>0.05);而各基因型受者TAC每日给药剂量和C/D值,差异均有统计学意义(P<0.05)。其中*3/*3型(GG)受者TAC的C/D值高于*1/*1型(AA)和*1/*3型(AG)受者,而*1/*1型(AA)和*1/*3型(AG)受者TAC的C/D值差异无统计学意义(P>0.05)。不同基因型肝移植受者肝肾功能指标浓度水平差异无统计学意义(P>0.05)。结论CYP3A5基因多态性对稳定期肝移植受者TAC的药物浓度C/D值有显著影响,*3/*3型(GG)基因受者TAC的C/D值较高,且日常服用的TAC剂量较低;CYP3A5基因多态性对稳定期肝移植受者肝肾功能指标影响较小。
Objective To investigate the effects of cytochrome enzymeCYP3A5(rs776746)gene polymorphism on tacrolimus(TAC)concentration and liver and kidney function in stable liver transplantation recipients.Methods A total of 132 stable liver transplant recipients who underwent liver transplantation in our hospital from March 2015 to June 2020 and received TAC based anti-rejection regimen and regular outpatient follow-up were selected.TheCYP3A5 genotype was detected by polymerase chain reaction restriction fragment length polymorphism and direct sequencing;the valley concentration of TAC in liver transplant recipients was detected by electrochemiluminescence magnetic particle immunoassay,and the standardized blood concentration(C/D)corrected by body mass and daily dose was calculated;the indexes of liver and kidney function in liver transplant recipients were detected by enzyme method or rate method.Results Among 132 liver transplant recipients,the number(frequency)ofCYP3A5*1/*1(AA),*1/*3(AG)and*3/*3(GG)were respectively 9 cases(9.85%),51 cases(38.64%)and 68 cases(51.51%).The frequencies of alleles*1(A)and*3(G)were respectively 29.17%and70.83%.The frequencies of each genotype accorded with Hardy Weinberg genetic balance(χ^(2)=3.67,P>0.05).There was no statistical significance on the difference in TAC valley concentration among different genotypes(P>0.05);the difference in daily dose of TAC and C/D value of each genotype were statistically significant(P<0.05).The C/D value of TAC in*3/*3(GG)recipients was higher than that in*1/*1(AA)and*1/*3(AG)recipients,but there was no statistical significance in the difference between*1/*1(AA)and*1/*3(AG)recipients(P>0.05).There was no statistical significance on the difference in the concentration of liver and kidney function indexes among different genotypes(P>0.05).Conclusion CYP3A5 gene polymorphism has a significant effect on the C/D value of TAC in stable liver transplantation recipients.The C/D value of TAC in*3/*3(GG)gene recipients is higher and the daily TAC dose is lower;CYP3
作者
刘珍
王峰
高晖
孙倩
应欣宇
LIU Zhen;WANG Feng;GAO Hui;SUN Qian;YING Xin-yu(Clinical Laboratory,Ningbo Medical Center Lihuili Hospital,Ningbo,Zhejiang 315040,China)
出处
《中国卫生检验杂志》
CAS
2022年第18期2248-2251,2256,共5页
Chinese Journal of Health Laboratory Technology
基金
浙江省医药卫生科技计划资助项目(2021KY304)。
关键词
CYP3A5基因
他克莫司
肝移植
稳定期
肝肾功能
CYP3A5 gene
Tacrolimus
Liver transplantation
Stable period
Liver and kidney function
