Meta-analysis of the associations of CYP2B6-516G>T polymorphisms with efavirenz-induced central nervous system side effects and virological outcome in HIV-infected adults
Meta-analysis of the associations of CYP2B6-516G>T polymorphisms with efavirenz-induced central nervous system side effects and virological outcome in HIV-infected adults
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DOI：
10.1038/s41397-019-0112-2
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发表时间：
2020-04-01
影响因子：
2.8
通讯作者：
Sun, Fengjun
中科院分区：
文献类型：
--
作者：
Cheng, Lin;Wang, Yu;Sun, Fengjun
关于细胞色素P450（CYP 2）B6 516 G>T多态性与HIV感染成人中依法韦仑诱导的中枢神经系统（CNS）副作用和病毒学应答之间关系的临床数据存在争议。我们试图通过荟萃分析来分析这些关联。为了识别合格的研究，我们系统地检索了PubMed、Embase、ScienceDirect和Web of Science。相关性的强度通过比值比（OR）和效应量（ES）以及95%置信区间（CI）来衡量。纳入了17项研究，共包括3598名艾滋病毒感染的成年人。结果显示，与GT和TT基因型相比，CYP 2B 6 -516 GG基因型与依法韦仑诱导的CNS副作用风险降低显著相关（GG + GT vs. TT：OR = 0.60，95% CI = 0.41-0.87，P = 0.006; GG vs. GT + TT：OR = 0.68，95% CI = 0.51-0.91，P = 0.008; GG vs. GT：OR = 0.70，95%CI = 0.51-0.94，P = 0.018），GT与TT之间无显著相关性（GT vs. TT：OR = 0.82，95%CI = 0.54-1.26，P = 0.372）。然而，CYP 2B 6 -516 GG和GT + TT基因型在病毒学应答方面无显著相关性（GT + TT vs. GG：ES = 1.06，95%CI = 0.95-1.18，P = 0.321; OR = 1.01，95%CI = 0.65-1.58，P = 0.963）。综上所述，我们的结果表明，与正常的依法韦仑清除基因型CYP 2B 6 -516 GG相比，依法韦仑清除缓慢和非常缓慢的基因型GT和TT与依法韦仑诱导的CNS副作用的风险增加显著相关，但与病毒学应答增加无关。根据HIV感染者CYP 2B 6 -516基因多态性情况调整依非韦伦的用药剂量，可促进患者对依非韦伦的耐受性。
Clinical data on the relationships of cytochrome P450 (CYP2) B6 516G>T polymorphisms with efavirenz-induced central nervous system (CNS) side effects and virological response in HIV-infected adults are controversial. We sought to analyze the associations by meta-analysis. To identify eligible studies, we systematically searched PubMed, Embase, ScienceDirect, and Web of Science. The strength of the associations was measured by odds ratio (OR) and effect size (ES) with 95% confidence interval (CI). Seventeen studies comprising a total of 3598 HIV-infected adults were included. The results showed that the CYP2B6-516 GG genotype was significantly associated with a decreased risk of efavirenz-induced CNS side effects compared with the GT and TT genotypes (GG + GT vs. TT: OR = 0.60, 95% CI = 0.41-0.87, P = 0.006; GG vs. GT + TT: OR = 0.68, 95% CI = 0.51-0.91, P = 0.008; GG vs. GT: OR = 0.70, 95% CI = 0.51-0.94, P = 0.018), and there was no significant association between the genetic variants GT and TT (GT vs. TT: OR = 0.82, 95% CI = 0.54-1.26, P = 0.372). However, there was no significant association between CYP2B6-516 GG and GT + TT genotypes in virological response (GT + TT vs. GG: ES = 1.06, 95% CI = 0.95-1.18, P = 0.321; OR = 1.01, 95% CI = 0.65-1.58, P = 0.963). Taken together, our results demonstrated that compared with the normal efavirenz clearance genotype CYP2B6-516 GG, the slow and very slow efavirenz clearance genotypes GT and TT were significantly associated with an increased risk of efavirenz-induced CNS side effects but not an increased virological response. To promote the tolerance of efavirenz, it is better to adjust the dosage of efavirenz according to the polymorphisms of CYP2B6-516 in HIV-infected adults.