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  

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

作　　者：李海菊[1,2] 平卫伟[3] 宋丽华[1] 郭春花[1] 郑王巧[1] 

机构地区：[1]山西长治医学院药学系,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 [3]山西长治医学院预防医学教研室,山西省长治市046000

出　　处：《中国组织工程研究》2012年第53期10037-10042,共6页Chinese Journal of Tissue Engineering Research

基　　金：山西省高校科技研究开发项目(200611034)~~

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=0.0006);亚组分析显示,肾移植后患者多药耐药基因13435CC的环孢素A剂量调整谷浓度显著低于CT基因型(P<0.00001)及TT基因型(P=0.0003);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。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 a

关 键 词：多药耐药基因1C3435T 基因多态性 环孢素A 药物动力学 META分析 

分 类 号：R318[医药卫生—生物医学工程]