细胞色素P450对肝移植患者他克莫司应用影响的临床研究

肝脏 ›› 2021, Vol. 26 ›› Issue (7): 779-782.

细胞色素P450对肝移植患者他克莫司应用影响的临床研究

周霞, 汤汝佳, 贺希, 高银杰, 姚红, 刘振文, 王洪波, 刘鸿凌

100039 北京解放军总医院第五医学中心肝病医学部

收稿日期:2020-12-20 出版日期:2021-07-31 发布日期:2021-09-02
通讯作者: 王洪波,Email:chfwyb@sina.com;刘鸿凌, Email:lhl7125@sina.com
作者简介:共同第一作者:汤汝佳
基金资助:
首都市民健康培育(Z161100000116058)

Clinical study of the effect of cytochrome P450 on the application of tacrolimus in liver transplantation recipients

ZHOU Xia, TANG Ru-jia, HE Xi, GAO Yin-jie, Yao Hong, LIU Zhen-wen, WANG Hong-bo, LIU Hong-ling

Liver Disease Department, the 5th Medical Center of the PLA General Hospital, Beijing, 100039China

Received:2020-12-20 Online:2021-07-31 Published:2021-09-02
Contact: WANG Hong-bo, Email:chfwyb@sina.com;LIU Hong-ling, Email:lhl7125@sina.com

摘要/Abstract

摘要： 目的观察肝移植患者的细胞色素P450(CYP)多态性规律以及对他克莫司应用的影响。方法选择2016年4月至2019年3月在解放军总医院第五医学中心接受肝移植并存活超过1个月的患者146例,随机分为实验组和对照组。对照组常规检测FK506谷浓度、生化指标等,并观察其临床特点。实验组患者在上述基础上,检测CYP3A4*1B、CYP3A5*3基因单核苷酸多态性。比较两组患者的给药剂量、FK506谷浓度、Co/D值。结果实验组和对照组患者的FK506谷浓度、C0/D值、肾损害、急性排异反应、感染发生率和病死率等无明显差异。在实验组73例患者中,CYP3A4*1B均为野生型。CYP3A5*3检测分型:A/G野生型 35例(46.1%);G/G突变型 33例(43.4)%;A/A 突变型5例(6.6%)。G/G突变患者C0/D值在多个时间点均明显高于A/G野生型和A/A突变型患者(术后3、6和12个月P值分别为0.002、0.007和0.034),FK506浓度无明显差异。实验组中G/G突变患者感染的发病率明显高于A/G野生型患者(χ²=7.066, P=0.008)。结论 CYP3A4*1B基因型在我国以野生型为主,对肝移植患者FK506代谢的影响较少。CYP3A5*3的基因多态性与他克莫司代谢密切相关,变异型患者可能需要较低剂量的他克莫司以达到目标浓度和降低感染的发生。

关键词: 他克莫司, 细胞色素P450, 基因多态性, 肝移植

Abstract: Objective To observe the regularity of cytochrome P450 (CYP) polymorphism in liver transplantation patients and its influence on the application of tacrolimus. Methods From April 2016 to March 2019, 146 patients who received liver transplantation in our hospital and survived for more than 1 month were selected and randomly divided into experimental group and control group. The patients in control group routinely detected FK506, biochemical indicators and observed its clinical characteristics. On the basis of the above items, the patients in experimental group were tested for CYP3A4*1B and CYP3A5*3 gene single nucleotide polymorphisms. Results There were no significant differences in the FK506 level, C0/D value, renal damage, acute rejection, infection and mortality between the experiment and the control group. Among the 73 recipients in the experiment group, CYP3A4*1B were all wild-type. CYP3A5*3 detection type: 35 patients were found A/G wild type (46.1%); 33 cases G/G mutant type (43.4) %; 5 cases A/A mutant type (6.6%). The C0/D value in G/G mutation patients was significantly higher than that of A/G wild-type and A/A mutant patients (P=0.002, 0.007 and 0.034 at 3, 6 and 12 months after surgery).There was no significant difference in FK506 level between groups. The incidence of infection in patients with G/G mutation in the experiment group was significantly higher than that in A/G wild-type patients (χ²=7.066, P=0.008). Conclusion The CYP3A4*3 genotype is mainly wild type in China, and it has little effect on FK506 metabolism. The genetic polymorphism of CYP3A5*3 is closely related to the metabolism of tacrolimus, and variant patients may need a lower dose of tacrolimus to reach the target level and reduce the incidence of infection.

Key words: Tacrolimus, Cytochrome P450, Genetic polymorphism, Liver transplantation

周霞, 汤汝佳, 贺希, 高银杰, 姚红, 刘振文, 王洪波, 刘鸿凌. 细胞色素P450对肝移植患者他克莫司应用影响的临床研究[J]. 肝脏, 2021, 26(7): 779-782.

ZHOU Xia, TANG Ru-jia, HE Xi, GAO Yin-jie, Yao Hong, LIU Zhen-wen, WANG Hong-bo, LIU Hong-ling. Clinical study of the effect of cytochrome P450 on the application of tacrolimus in liver transplantation recipients[J]. Chinese Hepatolgy, 2021, 26(7): 779-782.

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