中国组织工程研究

中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (53): 10037-10042.doi: 10.3969/j.issn.2095-4344.2012.53.030

• 器官移植循证医学 evidence-based medicine of organ transplantation • 上一篇    下一篇

多药耐药基因1 C3435T基因多态性对环孢素A药物动力学影响的Meta分析

李海菊1, 2，平卫伟3，宋丽华1，郭春花1，郑王巧1   

  1. 山西长治医学院，1药学系，3预防医学教研室，山西省长治市 046000
    2山西长治医学院附属和平医院药剂科，山西省长治市 046000
  • 收稿日期:2012-04-05 修回日期:2012-04-18 出版日期:2012-12-30 发布日期:2012-12-30
  • 通讯作者: 宋丽华，硕士，教授，山西长治医学院药学系，山西省长治市 046000 slh10282001@ yahoo.com.cn
  • 作者简介:李海菊★，女，1974年生，山西省长治县人，汉族，2005年中南大学湘雅医学院毕业，硕士，讲师，主要从事临床药学与临床药理学研究。 li_haiju@126. com

Effect of multi-drug resistance gene-1 C3435T genetic polymorphism on the concentration of cyclosporine A pharmacokinetics: A Meta-analysis

Li Hai-ju1, 2, Ping Wei-wei3, Song Li-hua1, Guo Chun-hua1, Zheng Wang-qiao1   

  1. 1Department of Pharmacy, 3Department of Preventive Medicine, Changzhi Medical College, Changzhi 046000, Shanxi Province, China
    2Department of Pharmacy, the Affiliated Heping Hospital of Changzhi Medical College, Changzhi 046000, Shanxi Province, China
  • Received:2012-04-05 Revised:2012-04-18 Online:2012-12-30 Published:2012-12-30
  • Contact: Song Li-hua, Master, Professor, Department of Pharmacy, Changzhi Medical College, Changzhi 046000, Shanxi Province, China slh10282001@ yahoo.com.cn
  • About author:Li Hai-ju★, Master, Lecturer, Department of Pharmacy, Changzhi Medical College, Changzhi 046000, Shanxi Province, China; Department of Pharmacy, the Affiliated Heping Hospital of Changzhi Medical College, Changzhi 046000, Shanxi Province, China li_haiju@126.com

PDF

564

被引次数

8

摘要：

背景：多药耐药基因1 C3435T基因多态性影响着P-糖蛋白的功能和表达，从而影响环孢素A血药浓度，产生个体差异。目前多药耐药基因1 C3435T基因多态性对环孢素A药物动力学影响的研究结果不一。
目的：基于国内外报道的国内相关研究，系统评价多药耐药基因1 C3435T基因多态性与环孢素A药物动力学的关系。
方法：计算机检索Cochrane图书馆、Medline、Plumbed、CNKI、万方等数据库，并辅以文献追溯的方法，收集国内外公开发表的国内相关病例对照、队列研究。检索年限均为从建库至2011-12-31。按纳入、排除标准筛选文献并评价纳入研究的质量后，采用RevMan 5.1软件进行Meta分析。
结果与结论：共纳入9篇文献，合计893例患者。Meta分析结果表明，多药耐药基因1 3435CC的环孢素A剂量调整谷浓度显著低于CT基因型(P=0.007)和TT基因型(P=0.000 6)；亚组分析显示，肾移植后患者多药耐药基因1 3435CC的环孢素A剂量调整谷浓度显著低于CT基因型 (P < 0.000 01)及TT基因型(P=0.000 3)；血液系统疾病患者多药耐药基因1 3435CC的环孢素A剂量调整谷浓度显著低于TT基因型(P=0.004)。多药耐药基因1 3435CC的环孢素A剂量调整峰浓度显著低于TT基因型(P=0.005)。提示多药耐药基因1 C3435T基因多态性对环孢素A血药浓度有影响，CC基因型患者血药浓度低于TT基因型。还需要大样本、前瞻性研究来探讨多药耐药基因1 C3435T基因多态性与环孢素A药物动力学的关系。

关键词: 多药耐药基因1 C3435T, 基因多态性, 环孢素A, 药物动力学, Meta分析

Abstract:

BACKGROUND: Multi-drug resistance gene-1 C3435T genetic polymorphism can influence the function and expression of P-glycoprotein, thus affecting the blood concentration of cyclosporine A, and lead to individual differences. The current studies of the influence of multi-drug resistance gene-1 C3435T genetic polymorphism on the concentration of cyclosporin A pharmacokinetics are inconsistent.
OBJECTIVE: To evaluate the effect of multi-drug resistance gene-1 C3435T genetic polymorphism on the concentration of cyclosporine A pharmacokinetics according to the domestic studies.
METHODS: Case-control studies and cohort studies were collected by searching Cochrane library, Medline database, PubMed database, CNKI database and Wanfang database and supplemented by literature retrospective method from building to 2011-12-31. All the relevant studies were identified and the quality of the included studies was assessed. The RevMan 5.1 software was used for Meta-analysis.
RESULTS AND CONCLUSION: Nine studies with 893 patients were included. The results of Meta-analysis showed that the dose-adjusted c0 level of cyclosporine A of multi-drug resistance gene-1 3435CC genotype was lower than of the CT genotype (P=0.007) and TT genotype (P=0.000 6). The subgroup analysis found that the dose-adjusted c0 level of multi-drug resistance gene-1 3435CC genotype was lower than that of CT genotype (P < 0.000 01) and TT genotype (P=0.000 3) in the patients after renal transplantation. The dose-adjusted c0 level of multi-drug resistance gene-1 3435CC genotype was lower than that of TT genotype (P=0.004) in the patients with hematological diseases. The dose-adjusted c2 level of the multi-drug resistance gene-1 3435CC genotype was lower than that of the TT genotype (P=0.005). The multi-drug resistance gene-1 C3435T genetic polymorphism can influence the blood concentration of cyclosporine A, and the blood concentration of multi-drug resistance gene-1 3435CC genotype was lower than that of TT genotype. High quality and large scale prospective trials are required to study the influence of multi-drug resistance gene-1 C3435T genetic polymorphism on cyclosporine A pharmacokinetics.

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