MTOR 基因变异与严重的 COVID-19 结果相关：一项多中心研究。
MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study.
发表日期：2023 Nov 09
作者：
Bruna Ramos Tosta, Ingrid Marins de Almeida, Laiane da Cruz Pena, Hatilla Dos Santos Silva, Fabiane S Reis-Goes, Nívia N Silva, João Victor Andrade Cruz, Mailane Dos Anjos Silva, Jéssica Francisco de Araújo, Juliana Lopes Rodrigues, Gabriella Oliveira, Ricardo Gassmann Figueiredo, Sara Nunes Vaz, Iris Montaño-Castellón, Daniele Santana, Fabyan Esberard de Lima Beltrão, Valdirene Leão Carneiro, Gubio Soares Campos, Carlos Brites, Vitor Fortuna, Camila Alexandrina Figueiredo, Soraya Castro Trindade, Helton Estrela Ramos, Ryan Dos Santos Costa
来源：
CYTOKINE & GROWTH FACTOR REVIEWS
摘要：
与严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染相关的最坏结果归因于细胞因子风暴，它对该疾病的免疫发病机制有重要影响。哺乳动物雷帕霉素靶点 (mTOR) 通路对于协调先天免疫细胞防御（包括细胞因子的产生）至关重要，并且在严重的 2019 冠状病毒病 (COVID-19) 个体中失调。个体遗传背景可能在加剧的免疫反应中发挥作用。在这项研究中，我们旨在调查 MTOR 基因变异与 COVID-19 结果之间的关联。这项研究招募了患有严重 (n = 285) 和轻度 (n = 285) 的个体组。 n = 207) 来自巴西各州的 COVID-19。对 MTOR 变体 rs1057079 和 rs2536 进行了基因分型。进行逻辑回归分析和 Kaplan-Meier 生存曲线。我们应用基因分型风险评分来估计风险等位基因的累积贡献。还测量了肿瘤坏死因子 (TNF) 和白细胞介素 6 (IL-6) 血浆水平。MTOR rs1057079 变体的 T 等位基因与患最严重形式的 COVID-19 的可能性较高相关。此外，较高水平的 IL-6 和 COVID-19 死亡与 rs2536 变体的 T 等位基因有关。这些变异在集体遗传时表现出累积风险。这些结果显示了 MTOR 基因变异的潜在致病作用，可能有助于预测 COVID-19 感染后的严重后果，从而更有效地分配卫生资源。版权所有 © 2023 Elsevier B.V.版权所有。
The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response.In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes.This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured.The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively.These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.Copyright © 2023 Elsevier B.V. All rights reserved.