中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (5): 806-809.doi: 10.3969/j.issn.1673-8225.2011.05.011

• 肾移植 kidney transplantation • 上一篇    下一篇

CYP3A5基因多态性与肾移植后钙调神经蛋白抑制剂慢性肾毒性的相关性

石  磊，保泽庆，朱云松，曾晓辉，龚丽娴，姚丽雯，赵树进   

  1. 解放军广州军区广州总医院药学部，广东省广州市 510010
  • 收稿日期:2010-07-18 修回日期:2010-12-31 出版日期:2011-01-29 发布日期:2011-01-29
  • 通讯作者: 赵树进，博士，教授，主任医师。解放军广州军区广州总医院药学部，广东省广州市 510010 gzzsjzhs@163.com
  • 作者简介:石磊★，女，1962年生，河北省唐山市人，汉族，1991年北京大学(原北京医科大学)毕业，硕士，教授，主任医师，主要从事临床药理学方面的研究。 zmj012@sohu.com
  • 基金资助:

    广东省科技计划项目社会发展计划(2005B30701004)。

Correlation between CYP3A5 genetic polymorphism and calcineurin inhibitor-induced chronic nphrotoxicity following renal transplantation

Shi Lei, Bao Ze-qing, Zhu Yun-song, Zeng Xiao-hui, Gong Li-xian, Yao Li-wen, Zhao Shu-jin   

  1. Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Area Command of Chinese PLA, Guangzhou  510010, Guangdong Province, China
  • Received:2010-07-18 Revised:2010-12-31 Online:2011-01-29 Published:2011-01-29
  • Contact: Zhao Shu-jin, Doctor, Professor, Chief physician, Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Area Command of Chinese PLA, Guangzhou 510010, Guangdong Province, China gzzsjzhs@163.com
  • About author:Shi Lei★, Master, Professor, Chief physician, Department of Pharmacy, Guangzhou General Hospital of Guangzhou Military Area Command of Chinese PLA, Guangzhou 510010, Guangdong Province, China zmj012@sohu.com
  • Supported by:

    the Society Plan of Science and Technology Project of Guangdong Province, No. 2005B30701004*

PDF

429

被引次数

9

摘要：

背景：钙调神经蛋白抑制剂是实体器官移植后抗排斥治疗中最重要的一线药物之一，主要通过包括CYP3A5在内的CYP3A亚家族进行代谢。但关于CYP3A5基因多态性与钙调神经蛋白抑制剂慢性肾毒性的相关研究国内外鲜有报道。
目的：观察CYP3A5基因多态性与中国人群中钙调磷酸酶抑制剂慢性肾毒性发生的关系。
方法：分别收集200例肾移植后出现慢性肾毒性的中国人种患者设为肾毒组；200例肾移植至少12个月后没有出现慢性肾毒性的中国人种患者设为对照组，取两组血样和临床数据。采用聚合酶链反应-限制性内切酶片段长度多态性技术分别检测两组的CYP3A5突变位点基因型。通过统计学分析CYP3A5的基因多态性与钙调神经蛋白抑制剂慢性肾毒性之间的关系。
结果与结论：慢性肾毒组中CYP3A5基因型*1/*1+*1/*3(显示CYP3A5活性)和*3/*3(不显示CYP3A5活性)分别占39.5%(79/200)和60.5%(121/200)；对照组中CYP3A5基因型*1/*1+*1/*3(显示CYP3A5活性)和*3/*3(不显示CYP3A5活性)分别占28.5%(57/200)和71.5%(143/200)。两组间差异有显著性意义(χ2=9.000，P < 0.05，OR=1.638，95%CI=1.078-2.488)。通过Logistic回归分析CYP3A5*1/*1和CYP3A5*1/*3是显著的引起CNI慢性肾毒性的危险因素(P < 0.05，OR=1.638，95%CI=1.078~2.488)。提示，CYP3A5的基因多态性可能增加肾移植患者慢性肾毒性的遗传易感性；参与钙调神经蛋白抑制剂慢性肾毒性疾病的发生。

关键词: 慢性肾毒性, 钙调神经蛋白抑制剂, CYP3A5, 基因多态性, 相关性

Abstract:

BACKGROUND: Calcineurin inhibitor is one of the important first-line drugs utilized in antirejection therapy following organ transplantation, which performed metabolism in CYP3A subfamily comprising CYP3A5. However, the correlation between CYP3A5 genetic polymorphism and calcineurin inhibitor-induced chronic nphrotoxicity remains poorly understood.     
OBJECTIVE: To observe the relationship between CYP3A5 genetic polymorphism calcineurin inhibitor-induced chronic nphrotoxicity in Chinese population.
METHODS: Blood samples and clinical data were collected from 200 Chinese patients with calcineurin inhibitor drug-induced chronic nephrotoxicity and 200 Chinese kidney allograft recipients without chronic nephrotoxicity as the controls. DNA was extracted from the blood samples, and the frequencies of CYP3A5 genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the polymorphisms of CYP3A5 and the calcineurin inhibitor drug-induced chronic nephrotoxicity was analyzed.
RESULTS AND CONCLUSION: The frequencies of the 3 gene types CYP3A5 *1/*1, *1/*3, and *3/*3 were 51% (102/200), 34.5% (69/200) and 14.5% (29/200) respectively in patients with calcineurin inhibitor drug-induced chronic nephrotoxicity, and 49.5% (99/200), 45% (90/200), and 5.5% (11/200), respectively in the control group. A statistical difference was found between the cases and the controls (χ2 = 9.000, P < 0.05, OR = 1.638, 95%CI = 1.078 – 2.488). Logistic regression analysis showed that the polymorphism of CYP3A5*1/*1 and CYP3A5*1/*3 remained a significant independent risk factor for calcineurin inhibitor drug-induced chronic nephrotoxicity after kidney allograft. Polymorphisms of CYP3A5 were found to be significantly associated with the risk of calcineurin inhibitor drug-induced chronic nephrotoxicity, possibly as a result of higher concentrations of toxic metabolites.

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