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更新时间：2023-03-01

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- China Pharmacy Vol. 30, Issue 20, (2019)
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PENG Ying, ZHANG Jun, LIU Ruming, et al. [J]. China Pharmacy 30(20).(2019)
DOI：

PENG Ying, ZHANG Jun, LIU Ruming, et al. [J]. China Pharmacy 30(20).(2019) DOI：

摘要

目的：系统评价CYP3A5 6986A＞G基因多态性与中国肾移植术后患者环孢素A（CsA）血药浓度的相关性。方法：计算机检索Cochrane图书馆、PubMed、Embase、中国生物医学文献数据库、中国期刊全文数据库、维普数据库、万方数据库等，收集肾移植术后使用CsA免疫抑制治疗并进行血药浓度监测的中国患者的病例对照研究或队列研究。筛选文献、提取资料后，采用纽卡斯渥太华量表评分对纳入文献质量进行评价，采用Rev Man 5.3软件进行Meta分析。结果：共纳入8篇文献，均为队列研究，共计890例患者。Meta分析结果显示，CYP3A5*1/*1型患者CsA剂量校正后的谷浓度（C0/D）显著低于CYP3A5*1/*3型[MD＝－6.97，95％CI（－13.18，－0.76），P＝0.03]；亚组分析结果显示，肾移植术后CsA检测时间≤1个月时[MD＝－8.50，95％CI（－12.57，－4.43），P＜0.000 1]、检测时间＞1～＜6个月时[MD＝－14.02，95％CI（－26.28，－1.76），P＝0.02]CYP3A5*1/*1型患者CsA的C0/D均显著低于CYP3A5*1/*3型患者。CYP3A5*1/*3型患者CsA的C0/D显著低于CYP3A5*3/*3型患者[MD＝－6.04，95％CI（－8.99，－3.09），P＜0.000 1]；亚组分析结果显示，肾移植术后CsA检测时间≤1个月时CYP3A5*1/*3型患者CsA的C0/D显著低于CYP3A5*3/*3型[MD＝－6.94，95％CI（－10.21，－3.68），P＜0.000 1]。CYP3A5*1/*1型患者CsA的C0/D显著低于CYP3A5*3/*3型[MD＝－12.64，95％CI（－21.09，－4.20），P＝0.003]；亚组分析结果显示，肾移植术后CsA检测时间≤1个月时[MD＝－16.69，95％CI（－24.03，－9.36），P＜0.000 01]、检测时间＞1～＜6个月时[MD＝－16.78，95％CI（－28.63，－4.93），P＝0.006]CYP3A5*1/*1型患者CsA的C0/D显著低于CYP3A5*3/*3型。CYP3A5*1/*1型与CYP3A5*1/*3型、CYP3A5*1/*3型与CYP3A5*3/*3型、CYP3A5*1/*1型与CYP3A5*3/*3型患者CsA剂量校正后的峰浓度比较，差异均无统计学意义。结论：CYP3A5 6986A＞G基因多态性与中国肾移植术后患者CsA的C0/D具有一定的相关性，且在肾移植术后CsA检测时间≤1个月时的大小顺序为CYP3A5*1/*1型＜CYP3A5*1/*3型＜CYP3A5 *3/*3型，检测时间＞1～＜6个月时为CYP3A5*1/*1型＜CYP3A5*1/*3型、CYP3A5*1/*1型＜CYP3A5*3/*3型。

Abstract

OBJECTIVE： To systematically evaluate the correlation between CYP3A5 6986A＞G gene polymorphism and blood concentration of Cyclosporine A （CsA） in Chinese renal transplant recipients. METHODS： Retrieved from Cochrane Library， PubMed， Embase， CBM， CNKI， VIP and Wanfang database， case-control or cohort studies about Chinese patients receiving CsA immunosuppressive therapy and blood concentration monitoring after kidney transplantation were collected. After literature screening and data extracting， the quality of literature was evaluated with Newcastle Ottawa scale， and Meta-analysis was performed by using Rev Man 5.3 software. RESULTS： Eight literatures with a total of 890 patients were involved in cohort study. Meta-analysis showed that the trough concentration after dosage correction （C0/D） of CsA in CYP3A5*1/*1 genotype was significantly lower than CYP3A5*1/*3 genotype[MD＝－6.97，95％CI （－13.18，－0.76），P＝0.03]. The subgroup analysis showed that the C0/D of CsA in CYP3A5*1/*1 genotype was significantly lower than CYP3A5*1/*3 genotype when test time≤1 month after renal transplant [MD＝－8.50，95％CI（－12.57，－4.43），P＜0.000 1] and ＞1-＜6 months after renal transplant [MD＝－14.02，95％CI（－26.28，－1.76），P＝0.02]. C0/D of CsA in CYP3A5*1/*3 genotype was significantly lower than CYP3A5*3/*3 genotype [MD＝－6.04，95％CI（－8.99，－3.09），P＜0.000 1]. The subgroup analysis showed that C0/D of CsA in CYP3A5*1/*3 genotype was significantly lower than CYP3A5*3/*3 genotype when test time ≤1 month after renal transplant [MD＝－6.94，95％CI（－10.21，－3.68），P＜0.000 1]. C0/D of CsA in CYP3A5*1/*1 genotype was significantly lower than CYP3A5*3/*3 genotype [MD＝－12.64，95％CI（－21.09，－4.20），P＝0.003]. The subgroup analysis showed that C0/D of CsA in CYP3A5*1/*1 genotype was significantly lower than CYP3A5*3/*3 genotype when test time ≤1 month after renal transplant [MD＝－16.69，95％CI（－24.03，－9.36），P＜0.000 01] and ＞1-＜6 months after renal transplant [MD＝－16.78，95％CI（－28.63，－4.93），P＝0.006]. There was no statistical significance in CsA of peak concentration after dose correction between CYP3A5*1/*1 genotype and CYP3A5*1/*3 genotype， CYP3A5*1/*3 genotype and CYP3A5*3/*3 genotype， CYP3A5*1/*1 genotype and CYP3A5*3/*3 genotype. CONCLUSIONS： CYP3A5 6986A＞G gene polymorphism is associated with C0/D of CsA in Chinese renal transplantation recipients. The sequence of C0/D when test time ≤1 month after renal transplantation is as follows as CYP3A5*1/*1 genotype＜CYP3A5*1/*3 genotype＜CYP3A5*3/*3 genotype； during＞1-＜6 months after renal transplantation， C0/D of CsA in CYP3A5*1/*1 genotype＜CYP3A5*1/*3 genotype and CYP3A5*1/*1 genotype＜CYP3A5*3/*3 genotype.

关键词

CYP3A5 6986A＞G基因多态性环孢素A肾移植术血药浓度相关性Meta分析

Keywords

CYP3A5 6986A＞GGene polymorphismCyclosporine ARenal transplantationBlood concentrationCorrelationMeta-analysis

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