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新冠病毒疾病严重程度和死亡率的遗传决定因素:住院患者中的Alu 287 bp多态性及……表达

Genetic determinants of COVID-19 severity and mortality: Alu 287 bp polymorphism and , , expression in hospitalized patients.

作者信息

de Araújo João Locke Ferreira, Rossi Átila Duque, de Almeida Jessica Maciel, Alves Hugo José, Leitão Isabela de Carvalho, de Ávila Renata Eliane, Castiñeiras Anna Carla Pinto, Oliveira Jéssica da Silva, Galliez Rafael Mello, Tonini Marlon Daniel Lima, Faffe Débora Souza, Barroso Shana Priscila Coutinho Barroso, Resende Gustavo Gomes, Gonçalves Cássia Cristina Alves, Castiñeiras Terezinha Marta Pereira Pinto, Tanuri Amilcar, Teixeira Mauro Martins, Aguiar Renato Santana, Cardoso Cynthia Chester, de Souza Renan Pedra

机构信息

Departamento de genética, ecologia e evolução, Laboratório de biologia integrativa, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Departamento de biorregulação, Laboratório de imunofarmacologia e biologia molecular, Universidade Federal da Bahia, Salvador, BA, Brazil.

出版信息

PeerJ. 2025 Jan 20;13:e18508. doi: 10.7717/peerj.18508. eCollection 2025.

DOI:10.7717/peerj.18508
PMID:39850833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11756369/
Abstract

BACKGROUND

The angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are central human molecules in the SARS-CoV-2 virus-host interaction. Evidence indicates that may influence expression. This study aims to determine whether ACE1, ACE2, and TMPRSS2 mRNA expression levels, along with the ACE1 Alu 287 bp polymorphism (rs4646994), contribute to the severity and mortality of COVID-19.

METHODS

Swabs were collected in two Brazilian cities in 2020: Belo Horizonte ( = 134) and Rio de Janeiro ( = 41). A swab of mild patients in Rio de Janeiro who were not hospitalized ( = 172) was also collected. All analyzed biological material was obtained from residual diagnostic samples in 2020, prior to the emergence of SARS-CoV-2 variants of concern. , , and (reference gene) expression levels were evaluated in 40 cycles of quantitative PCR. Alu 287 bp polymorphism was genotyped using the FastStart Universal SYBR Green Master kit.

RESULTS

The median age differed between clinical sites ( = 0.016), but no difference in median days of hospitalization was observed ( = 0.329). Age was associated with severity ( = 0.014) and mortality ( = 0.014) in the Belo Horizonte cohort. No alteration in , and expression was associated with severity or mortality. polymorphism rs4646994 did not influence the likelihood of either outcome. A meta-analysis including available data from the literature showed significant effects: the D-allele conferred risk (OR = 1.39; 95% CI [1.12-1.72]).

摘要

背景

血管紧张素转换酶2(ACE2)和跨膜丝氨酸蛋白酶2(TMPRSS2)是严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒-宿主相互作用中的核心人类分子。有证据表明, 可能会影响 表达。本研究旨在确定血管紧张素转换酶1(ACE1)、ACE2和TMPRSS2的信使核糖核酸(mRNA)表达水平,以及ACE1 Alu 287碱基对多态性(rs4646994)是否会导致2019冠状病毒病(COVID-19)的严重程度和死亡率。

方法

2020年在巴西的两个城市采集样本:贝洛奥里藏特(n = 134)和里约热内卢(n = 41)。还采集了里约热内卢未住院的轻症患者的样本(n = 172)。所有分析的生物材料均取自2020年严重急性呼吸综合征冠状病毒2关注变体出现之前的残留诊断样本。在40个循环的定量聚合酶链反应(PCR)中评估ACE1、ACE2、TMPRSS2和GAPDH(参照基因)的表达水平。使用FastStart通用SYBR Green Master试剂盒对ACE1 Alu 287碱基对多态性进行基因分型。

结果

临床地点之间的年龄中位数存在差异(P = 0.016),但住院天数中位数未观察到差异(P = 0.329)。在贝洛奥里藏特队列中,年龄与严重程度(P = 0.014)和死亡率(P = 0.014)相关。ACE1、ACE2和TMPRSS2表达的改变与严重程度或死亡率无关。rs4646994多态性不影响任何一种结果的可能性。一项纳入文献中可用数据的荟萃分析显示有显著影响:D等位基因带来风险(优势比[OR] = 1.39;95%置信区间[CI][1.12 - 1.72])。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e6d/11756369/70c2bac428c8/peerj-13-18508-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e6d/11756369/3ee633001eae/peerj-13-18508-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e6d/11756369/70c2bac428c8/peerj-13-18508-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e6d/11756369/3ee633001eae/peerj-13-18508-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e6d/11756369/70c2bac428c8/peerj-13-18508-g002.jpg

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