Correlation Between CYP3A5 Gene Polymorphism and Tacrolimus Concentration/Dose Ratio in the Early Postoperative Period After Liver Transplantation

WANG Xin; WANG Huaguang; QIU Kui; AI Chao; LIU Lihong

doi:10.14009/j.issn.1672-2124.2022.01.012

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Correlation Between CYP3A5 Gene Polymorphism and Tacrolimus Concentration/Dose Ratio in the Early Postoperative Period After Liver Transplantation

更新时间：2022-10-08

- Correlation Between CYP3A5 Gene Polymorphism and Tacrolimus Concentration/Dose Ratio in the Early Postoperative Period After Liver Transplantation
- Vol. 22, Issue 1, Pages: 55-58(2022)
- 作者机构：
  
  1. 首都医科大学药学院
  2. 清华大学附属北京清华长庚医院药学部/清华大学临床医学院
  3. 首都医科大学附属北京朝阳医院药事部
  4. 中日友好医院药学部
- 作者简介：
- 基金信息：
- DOI：10.14009/j.issn.1672-2124.2022.01.012
  CLC： R657.3
- Published：2022，
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WANG Xin, WANG Huaguang, QIU Kui, et al. Correlation Between CYP3A5 Gene Polymorphism and Tacrolimus Concentration/Dose Ratio in the Early Postoperative Period After Liver Transplantation. [J]. 22(1):55-58(2022)
DOI：

WANG Xin, WANG Huaguang, QIU Kui, et al. Correlation Between CYP3A5 Gene Polymorphism and Tacrolimus Concentration/Dose Ratio in the Early Postoperative Period After Liver Transplantation. [J]. 22(1):55-58(2022) DOI： 10.14009/j.issn.1672-2124.2022.01.012.

摘要

目的:探讨供受体CYP3A5基因多态性对肝移植术后早期他克莫司浓度/剂量比（C/D）的影响。方法:回顾性收集2020年在清华大学附属北京清华长庚医院首次接受肝移植的患者71例

记录其术后2周、3周和4周时服用的他克莫司剂量及相应时间点的血药浓度（C）

得到每千克日剂量（D）

分别计算C/D。采用荧光原位杂交技术测定供受体CYP3A5的基因型

根据基因型进行分组

将CYP3A5

1和CYP3A5

3归为表达组

将CYP3A5

3归为非表达组

分别分析并联合分析供受体基因型对于C/D的影响

同时联合分析供受体基因型对于肝移植术后肝功能恢复正常率的影响。结果:术后2周、3周和4周时

供体和受体表达组的他克莫司C/D均低于非表达组

差异有统计学意义（P

0.05）。供受体联合分析结果显示

供体非表达/受体非表达组的他克莫司C/D高于供体表达/受体表达组、供体表达/受体非表达组和供体非表达/受体表达组

差异均有统计学意义（P

0.05）。术后1个月内

供体表达/受体表达组、供体表达/受体非表达组、供体非表达/受体表达组和供体非表达/受体非表达组组间肝功能恢复正常率比较

差异无统计学意义（P

0.05）。结论:供受体CYP3A5基因多态性均是影响肝移植术后患者他克莫司C/D的遗传因素

携带CYP3A5

3基因型的患者

在达到相同目标的血药浓度时可能需要更低的剂量

用药前进行基因型检测能够更有效地指导他克莫司的临床应用。

Abstract

OBJECTIVE: To investigate the effect of donor-recipient CYP3 A5 gene polymorphisms on the tacrolimus concentration/dose ratio（ C/D） in the early postoperative period after liver transplantation. METHODS:Seventy-one patients who received liver transplantation for the first time at Beijing Tsinghua Changgung Hospital

School of Clinical Medicine

Tsinghua University in 2020 were retrospectively collected. Tacrolimus dose at 2

3 and 4 weeks after surgery and blood concentration（ C） at corresponding time points were recorded to obtain daily dose per kilogram（ D）

and C/D value was calculated respectively. The genotypes of donor-recipient CYP3 A5 were determined by fluorescence in situ hybridization

and CYP3 A5

1 and CYP3 A5

3 were grouped according to genotype

and CYP3 A5

3 were grouped as the expression group and CYP3 A5

3 were grouped as the non-expression group

the effects of donor-recipient genotype on C/D value were analyzed separately and jointly

meanwhile

the donor-recipient genotypes were analyzed to compare the normal recovery rate of liver function after liver transplantation. RESULTS: At 2

3 and 4 weeks after surgery

C/D values were lower in both donor and recipient expressing group than in the non-expressing group

with statistically significant differences（ P

0. 05）. C/D values of donor non-expression/receptor non-expression group were higher than those of donor expression/receptor expression group

donor expression/receptor non-expression group and donor non-expression/receptor expression group

the difference was statistically significant（ P

0. 05）. At 1 month after surgery

there was no significant difference in the normal rate of liver function between donor expression/receptor expression group

donor expression/receptor nonexpression group

donor non-expression/receptor expression group and donor non-expression/receptor non-expression group（ P

0. 05）. CONCLUSIONS: Both donor-recipient CYP3 A5 gene polymorphisms are genetic factors affecting tacrolimus C/D in patients after liver transplantation. Patients carrying CYP3 A5

3 may require a lower dose to achieve the same target blood concentration

Genotype testing before medication can more effectively guide the clinical application of tacrolimus.

关键词

肝移植CYP3A5他克莫司基因多态性浓度/剂量比

Keywords

Liver transplantationCYP3A5TacrolimusGene polymorphismConcentration/dose ratio

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