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CYP3A5*3基因多态性对中国膜性肾病患者他克莫司血药浓度及疗效影响的Meta分析

Meta-analysis of the effects of CYP3A5*3 gene polymorphisms on tacrolimus blood concentration and effectiveness in Chinese patients with membranous nephropathy.

作者信息

Dai Xiaona, Yuan Fang, Chai Lan

机构信息

Department of Rheumatology and Immunology, Zhejiang Hospital, Hangzhou, Zhejiang, China.

出版信息

Front Pharmacol. 2024 May 21;15:1385322. doi: 10.3389/fphar.2024.1385322. eCollection 2024.

Abstract

OBJECTIVE

The study aimed to systematically evaluate the relationship between CYP3A5*3 gene polymorphisms and the blood concentration and effectiveness of tacrolimus (TAC) in patients with membranous nephropathy (MN).

METHODS

PubMed, Cochrane Library, Embase, Web of Science, China Biomedical, China National Knowledge Infrastructure, Wanfang, Vipshop, ReadShow, Clinical Trials Registry, and other databases were searched. Studies on the relationship between CYP3A5*3 gene polymorphism and TAC blood concentration in MN patients were collected, and meta-analysis was performed using Stata 16 software.

RESULTS

A total of eight publications were included in the study, including 498 MN patients. CYP3A53 gene polymorphisms are associated with tacrolimus blood levels in patients with MN. The results of the relationship between CYP3A53 genotype polymorphisms and tacrolimus blood trough concentrations of the AA + AG genotype were lower than those of the GG genotype at ≤1 month [WMD = -2.08, 95% CI (-2.57, -1.59), < 0.001] and 1-6 months [WMD = -0.63, 95% CI (-0.98, -0.27), < 0.001]; however, they were not statistically significant at ≥6 months ( = 0.211). Furthermore, the subgroup analysis revealed that the dose-adjusted concentration of tacrolimus (C0/D) of the AA + AG genotype was lower than that of the GG genotype at ≤1 month [SMD = -1.93, 95% CI (-2.79, -1.08), < 0.001], 1-6 months [SMD = -2.25, 95% CI (-2.71, -1.79), < 0.001], and ≥6 months [SMD = -2.36, 95% CI (-2.86, -1.86), < 0.001]. In addition, there was no statistically significant difference in effectiveness between the two groups at 3, 6, and 12 months of TAC administration ( > 0.05).

CONCLUSION

Serum TAC concentrations in MN patients were correlated with CYP3A53 genotype polymorphisms. Detection of the CYP3A53 genotype before the administration of TAC may provide some clinical value for optimizing the treatment of MN patients.

SYSTEMATIC REVIEW REGISTRATION

https://inplasy.com/, identifier [INPLASY202430083].

摘要

目的

本研究旨在系统评价细胞色素P450 3A5(CYP3A5)*3基因多态性与膜性肾病(MN)患者他克莫司(TAC)血药浓度及疗效之间的关系。

方法

检索PubMed、Cochrane图书馆、Embase、Web of Science、中国生物医学文献数据库、中国知网、万方数据库、维普资讯、读秀学术搜索、临床试验注册中心等数据库。收集关于CYP3A5*3基因多态性与MN患者TAC血药浓度关系的研究,并使用Stata 16软件进行荟萃分析。

结果

本研究共纳入8篇文献,包括498例MN患者。CYP3A53基因多态性与MN患者的他克莫司血药水平相关。CYP3A53基因型多态性与他克莫司血药谷浓度之间的关系结果显示,AA + AG基因型在≤1个月时低于GG基因型[加权均数差(WMD)=-2.08,95%置信区间(CI)(-2.57,-1.59),P<0.001],在1 - 6个月时也低于GG基因型[WMD=-0.63,95%CI(-0.98,-0.27),P<0.001];然而,在≥6个月时差异无统计学意义(P=0.211)。此外,亚组分析显示,AA + AG基因型的他克莫司剂量调整浓度(C0/D)在≤1个月时低于GG基因型[标准化均数差(SMD)=- .93,95%CI(-2.79,-1.08),P<0.001],在1 - 6个月时低于GG基因型[SMD=-2.25,95%CI(-2.71,-1.79),P<0.001],在≥6个月时也低于GG基因型[SMD=-2.36,95%CI(-2.86,-1.86),P<0.001]。此外,在TAC给药3、6和12个月时,两组疗效差异无统计学意义P>0.05)。

结论

MN患者血清TAC浓度与CYP3A53基因型多态性相关。在给予TAC前检测CYP3A53基因型可能为优化MN患者的治疗提供一定的临床价值。

系统评价注册

https://inplasy.com/,标识符[INPLASY202430083]

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd2d/11148365/7ffb5420d779/fphar-15-1385322-g001.jpg

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