吉林大学学报(医学版) ›› 2018, Vol. 44 ›› Issue (03): 537-542.doi: 10.13481/j.1671-587x.20180315

• 临床研究 • 上一篇    下一篇

CYP3A5基因多态性对肾移植术后患者他克莫司代谢的影响

王明睿1,2, 翟秀宇1, 王钢1, 张文岚1, 高宝山1, 周洪澜1, 傅耀文1   

  1. 1. 吉林大学第一医院泌尿系统疾病诊治中心, 吉林 长春 130021;
    2. 运城市中心医院泌尿外科, 山西 运城 044000
  • 收稿日期:2017-05-04 出版日期:2018-05-28 发布日期:2018-05-31
  • 通讯作者: 高宝山,副主任医师,硕士研究生导师(Tel:0431-81875831,E-mail:gaobaoshan@medmail.com.cn) E-mail:gaobaoshan@medmail.com.cn
  • 作者简介:王明睿(1990-),男,山西省运城市人,医师,医学硕士,主要从事泌尿系肿瘤和肾脏移植方面的研究。
  • 基金资助:
    国家自然科学基金青年基金资助课题(81501381)

Effects of CYP3A5 genetic polymorphisms on metabolism of tacrolimus in patients after kidney transplantation

WANG Mingrui1,2, ZHAI Xiuyu1, WANG Gang1, ZHANG Wenlan1, GAO Baoshan1, ZHOU Honglan1, FU Yaowen1   

  1. 1. Department of Urinary System Diseases Treatment Center, First Hospital, Jilin University, Changchun 130021, China;
    2. Department of Urinary Surgery, Yuncheng Central Hospital, Yuncheng 044000, China
  • Received:2017-05-04 Online:2018-05-28 Published:2018-05-31

摘要: 目的:探讨不同CYP3A5基因型对肾移植术后患者血他克莫司浓度的影响,为肾移植术后患者他克莫司个体化治疗提供依据。方法:回顾性分析115例肾移植术后患者的临床资料,根据CYP3A5基因型分为野生纯合子组(CYP3A5*1/*1型,11例)、突变杂合子组(CYP3A5*1/*3型,46例)和突变纯合子组(CYP3A5*3/*3型,58例),记录3组患者术后不同时间点(7d、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。结果:3组患者体质量指数(BMI)、年龄构成比和性别构成比比较差异均无统计学意义(P>0.05)。与突变杂合子组比较,野生纯合子组患者术后7d、3个月、1年和2年他克莫司C0/D值明显降低(P=0.011,P<0.01,P=0.022,P=0.024);与突变纯合子组比较,野生纯合子组和突变杂合子组患者术后各个时段他克莫司C0/D值均明显降低(P<0.01)。野生纯合子组术后7d患者他克莫司C0/D值明显低于术后6个月、1年和2年(P=0.004,P=0.049,P=0.036);突变杂合子组术后7d患者他克莫司C0/D值明显低于术后1个月、3个月、6个月、1年和2年(P=0.006,P<0.01,P<0.01,P<0.01,P<0.01),术后1个月患者他克莫司C0/D值明显低于术后6个月(P=0.013);突变纯合子组术后7d患者他克莫司C0/D值明显低于术后1个月、3个月、6个月、1年和2年(P=0.002,P<0.01,P<0.01,P<0.01,P<0.01)。结论:CYP3A5基因多态性对肾移植术后患者血他克莫司浓度有明显影响,且这种影响可持续至术后2年。

关键词: 肾移植, CYP3A5基因, 他克莫司, 基因多态性

Abstract: Objective: To investigate the effects of different CYP3A5 genotypes on the concentrations of tacrolimus in blood of the patients after kidney transplantation,and to provide the valuable evidence for personalized administration in the patients after kidney transplantation. Methods: The clinical materials of 115 patients after kidney transplantation were analyzed retrospectively.The patients were divided into three groups according to the CYP3A5 genotypes:CYP3A5*1/*1 group(11 cases), CYP3A5*1/*3 group(46 cases) and CYP3A5*3/*3 group(58 cases).The concentration/dosage (C0/D) values of tacrolimus in blood of the patients in three groups at 7 d,1 month,3 months,6 months,1 year, and 2 years after operation were detected,respectively. Results: The differences of body mass index(BMI),age composition ratios and gender composition ratios of the patients were not significant between three groups(P>0.05).Compared with CYP3A5*1/*3 group,the C0/D values of tacrolimus in blood of the patients in CYP3A5*1/*1 group at 7 d,3 months,1 year and 2 years after operation were decreased(P=0.011,P<0.01,P=0.022,P=0.024);compared with CYP3A5*3/*3 group,the C0/D values of tacrolimus in blood of the patients in CYP3A5*1/*1 group and CYP3A5*1/*3 group at 7 d, 1 months,3 months,6 months,1 year and 2 years after operation were decreased(P<0.01).In CYP3A5*1/*1 group,the C0/D value of tacrolimus in blood of the patients at 7 d after operation was significantly lower than those at 6 months,1 year and 2 years after operation (P=0.004,P=0.049,P=0.036); in CYP3A5*1/*3 group,the C0/D value of tacrolimus in blood of the patients at 7 d after operation was significantly lower than those at 1 month,3 months,6 months,1 year and 2 years after operation(P=0.006,P<0.01,P<0.01,P<0.01,P<0.01),and the C0/D value of tacrolimus in blood of the patients at 1 month after operation was significantly lower than that at 6 months after operation(P=0.013); in CYP3A5*3/*3 group,the C0/D value of tacrolimus in blood of the patients at 7 d after operation was significantly lower than those at 1 month,3 months,6 months,1 year and 2 years after operation(P=0.002,P<0.01,P<0.01,P<0.01,P<0.01). Conclusion: The CYP3A5 genetic polymorphism has a significant impact on the metabolism of tacrolimus in blood of the patients after kidney transplantation,and the impact could last for two years.

Key words: kidney transplantation, CYP3A5 genotype, tacrolimus, genetic polymorphism

中图分类号: 

  • R692.5