Meta-analysis of the effect of CYP2B6, CYP2A6, UGT2B7 and CAR polymorphisms on efavirenz plasma concentrations
Meta-analysis of the effect of CYP2B6, CYP2A6, UGT2B7 and CAR polymorphisms on efavirenz plasma concentrations
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DOI：
10.1093/jac/dkz329
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发表时间：
2019-11-01
影响因子：
5.2
通讯作者：
Owen, Andrew
中科院分区：
文献类型：
--
作者：
Ayuso, Pedro;Neary, Megan;Owen, Andrew
背景：依非韦伦的初级代谢由CYP2B6催化，CYP2A6少量参与。随后，I期代谢产物被UGT2B7偶联，并且组成型雄甾受体（CAR）已被证明可以转录调节许多相关的酶和转运蛋白。在一些但不是全部的研究中，这些蛋白质编码基因中出现的几种多态性已被证明会影响依非韦伦的药代动力学。目的：通过荟萃分析评估CYP2B6 rs3745274、CYP2A6 （rs28399454、rs8192726和rs28399433）、UGT2B7 （rs28365062和rs7439366）和NR1I3 （rs2307424和rs3003596）多态性对中剂量依非韦伦血药浓度的总体影响。方法：通过文献综述，收集药代动力学参数，并使用review Manager和openmeta - analyst对这些变异进行meta分析。共纳入28项研究。结果：不出所料，分析证实CYP2B6 rs3745274等位基因T纯合子个体的依非韦伦浓度显著高于G等位基因纯合子个体[加权标准平均差(WSMD)=2.98；95% ci 2.19-3.76；P
Background: Efavirenz primary metabolism is catalysed by CYP2B6 with minor involvement of CYP2A6. Subsequently, phase I metabolites are conjugated by UGT2B7, and constitutive androstane receptor (CAR) has been shown to transcriptionally regulate many relevant enzymes and transporters. Several polymorphisms occurring in the genes coding for these proteins have been shown to impact efavirenz pharmacokinetics in some but not all studies.Objectives: A meta-analysis was performed to assess the overall effect of CYP2B6 rs3745274, CYP2A6 (rs28399454, rs8192726 and rs28399433), UGT2B7 (rs28365062 and rs7439366) and NR1I3 (rs2307424 and rs3003596) polymorphisms on mid-dose efavirenz plasma concentrations.Methods: Following a literature review, pharmacokinetic parameters were compiled and a meta-analysis for these variants was performed using Review Manager and OpenMetaAnalyst. A total of 28 studies were included.Results: Unsurprisingly, the analysis confirmed that individuals homozygous for the T allele for CYP2B6 rs3745274 had significantly higher efavirenz concentrations than those homozygous for the G allele [weighted standard mean difference (WSMD)=2.98; 95% CI 2.19-3.76; P