CYP3A5基因多态性与肝移植患者他克莫司 血药浓度关系的Meta分析

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CYP3A5基因多态性与肝移植患者他克莫司血药浓度关系的Meta分析

张阳

昆明市第一人民医院

收稿日期:2015-10-19 修回日期:2015-12-03 出版日期:2015-12-25 发布日期:2015-12-25

CYP3A5 Genotypes and Blood Concentration of Tacrolimus in Liver Transplant Recipients：a Meta-analysis

First hospital of Kunming

Received:2015-10-19 Revised:2015-12-03 Online:2015-12-25 Published:2015-12-25

摘要/Abstract

摘要： 目的：系统性评价CYP3A5基因多态性与肝移植患者他克莫司(FK506)血药浓度的关系，为临床治疗提供循证参考。方法：计算机检索Medline、Embase、ScienceDirect、Pubmed、CNKI、Wanfang、VIP数据库，检索年限为1990年1月至2014年12月，收集有关亚洲人群CYP3A5基因多态性与肝移植患者FK506血药浓度关系的研究，提取资料并进行质量评价后，采用RevMan5.3软件进行Meta分析。结果：纳入文献共计9篇，包含848例患者。Meta分析结果显示，CYP3A5基因中GG型患者在肝移植供体术后2周[MD=-27.09，95%CI(-41.01，-13.16)，P＜0.05]、1个月[MD=-44.04，95%CI (-70.45，-17.63)，P=0.001]、3个月[MD=-82.12，95%CI(-112.72，-51.51)，P＜0.05]时，FK5O6血药浓度/剂量值高于同期AA AG基因型；CYP3A5基因中GG型在肝移植受体术后2周[MD=-18.14，95%CI(-34.32，-1.96)，P=0.03]、1个月[MD=-20.64，95%CI(-37.64，-3.63)，P=0.02]、3个月[MD=-25.88，95%CI(-42.22，-9.54)，P=0.002]、6个月[MD=-40.67，95%CI（-57.00，-24.34），P＜0.05]时，FK5O6血药浓度/剂量值高于同期AA AG基因型，CYP3A5基因型中GG基因型在肝移植受体术后3个月[MD=-19.59，95%CI(-37.06，-2.12)，P=0.003]时FK5O6血药浓度/剂量值高于同期AG基因型。结论：肝移植术后FK506血药浓度/剂量值与CYP3A5基因型相关，GG基因型患者的FK506血药浓度/剂量值明显较其他基因型患者高，因此在肝移植术后应用FK506作为治疗时，有必要对患者进行CYP3A5基因检测，以指导临床治疗。由于纳入研究数量较少、样本量不大，该结论有待大样本、高质量的研究进一步证实。

Abstract: Objective： To systematically review the correlation between CYP3A5 genotypes and blood concentration of tacrolimus (FK506) in liver transplant recipients.Methods： Such databases as Medline、 Embase、ScienceDirect、Pubmed、CNKI、 WanFang and VIP Data were electronically searched for studies about the correlation between CYP3A5 genotypes and FK506 (blood concentration/dose-respones relationship)in liver transplant recipients， from January 1990 to December 2014.According to the inclusion and exclusion criteria， literature was screened，data were extracted， and the methodological quality of included studies was also assessed. Then， Meta-analysis was performed using RevMan 5.3 software.Results： A total of 9 literatures were involved，including 848 patients.The results of Meta-analysis showed that 2 week [MD=-27.09，95%CI(-41.01，-13.16)， P<0.05] and 1 month [MD=-44.04， 95%CI (-70.45，-17.63)， P=0.001] and 3 months[MD＝-82.12，95%CI(-112.72，-51.51)， P<0.05]after liver transplant donor，the blood concentration/dose of FK506 in patients with CYP3A5 GG genotype was higher than in AA AG genotype； 2 week[MD=-18.14，95%CI(-34.32，-1.96)， P=0.03]，1 month [MD=-20.64，95%CI(-37.64，-3.63)， P=0.02]，3 months [MD=-25.88，95%CI(-42.22，-9.54)，P=0.002] and 6 months [MD=-40.67，95%CI(-57.00，-24.34)， P<0.05]after liver transplant recipient;the blood concentration/dose of FK506 in patients with CYP3A5 GG genotype was higher than in AA AG genotype;3 months [MD=-19.59，95%CI(-37.06，-2.12)，P=0.003]after liver transplant recipient，the blood concentration/dose of FK506 in patients with CYP3A5 GG genotype was higher than in AG genotype.Conclusion：The blood concentration/dose of FK506 is associated with CYP3A5 genotype in liver transplant recipients and donor.The blood concentration/dose of FK506 genotypes of GG patients was higher than the other genotypes.We propose that patients with liver transplantation should receive genetic testing to determine the use of FK506 as an immunosuppressor，so as to guide its clinical application.Due to small scale and number of included studies，more large-scale and high-quality studies are required for further validation.

张阳. CYP3A5基因多态性与肝移植患者他克莫司血药浓度关系的Meta分析[J]. .

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