Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients
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 ACE1 may influence ACE2 expression. This study aims to determine whether ACE1, ACE2, and TMPRSS2 mRNA...
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| author | João Locke Ferreira de Araújo Átila Duque Rossi Jessica Maciel de Almeida Hugo José Alves Isabela de Carvalho Leitão Renata Eliane de Ávila Anna Carla Pinto Castiñeiras Jéssica da Silva Oliveira Rafael Mello Galliez Marlon Daniel Lima Tonini Débora Souza Faffe Shana Priscila Coutinho Barroso Barroso Gustavo Gomes Resende Cássia Cristina Alves Gonçalves Terezinha Marta Pereira Pinto Castiñeiras Amilcar Tanuri Mauro Martins Teixeira Renato Santana Aguiar Cynthia Chester Cardoso Renan Pedra de Souza |
| author_facet | João Locke Ferreira de Araújo Átila Duque Rossi Jessica Maciel de Almeida Hugo José Alves Isabela de Carvalho Leitão Renata Eliane de Ávila Anna Carla Pinto Castiñeiras Jéssica da Silva Oliveira Rafael Mello Galliez Marlon Daniel Lima Tonini Débora Souza Faffe Shana Priscila Coutinho Barroso Barroso Gustavo Gomes Resende Cássia Cristina Alves Gonçalves Terezinha Marta Pereira Pinto Castiñeiras Amilcar Tanuri Mauro Martins Teixeira Renato Santana Aguiar Cynthia Chester Cardoso Renan Pedra de Souza |
| author_sort | João Locke Ferreira de Araújo |
| collection | DOAJ |
| description | 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 ACE1 may influence ACE2 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 (n = 134) and Rio de Janeiro (n = 41). A swab of mild patients in Rio de Janeiro who were not hospitalized (n = 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. ACE1, ACE2, TMPRSS2, and B2M (reference gene) expression levels were evaluated in 40 cycles of quantitative PCR. ACE1 Alu 287 bp polymorphism was genotyped using the FastStart Universal SYBR Green Master kit. Results The median age differed between clinical sites (p = 0.016), but no difference in median days of hospitalization was observed (p = 0.329). Age was associated with severity (p = 0.014) and mortality (p = 0.014) in the Belo Horizonte cohort. No alteration in ACE1, ACE2 and TMPRSS2 expression was associated with severity or mortality. ACE1 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]). |
| format | Article |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-fa5bd3d642c44c91b0ff6d0aea6ef7172025-01-22T15:05:11ZengPeerJ Inc.PeerJ2167-83592025-01-0113e1850810.7717/peerj.18508Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patientsJoão Locke Ferreira de Araújo0Átila Duque Rossi1Jessica Maciel de Almeida2Hugo José Alves3Isabela de Carvalho Leitão4Renata Eliane de Ávila5Anna Carla Pinto Castiñeiras6Jéssica da Silva Oliveira7Rafael Mello Galliez8Marlon Daniel Lima Tonini9Débora Souza Faffe10Shana Priscila Coutinho Barroso Barroso11Gustavo Gomes Resende12Cássia Cristina Alves Gonçalves13Terezinha Marta Pereira Pinto Castiñeiras14Amilcar Tanuri15Mauro Martins Teixeira16Renato Santana Aguiar17Cynthia Chester Cardoso18Renan Pedra de Souza19Departamento de genética, ecologia e evolução, Laboratório de biologia integrativa, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartamento de genética, Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de genética, Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de genética, ecologia e evolução, Laboratório de biologia integrativa, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilNúcleo de Enfrentamento e Estudos de Doenças Infecciosas Emergentes e Reemergentes (NEEDIER), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilHospital Eduardo de Menezes, Belo Horizonte, Minas Gerais, BrazilNúcleo de Enfrentamento e Estudos de Doenças Infecciosas Emergentes e Reemergentes (NEEDIER), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilMarinha do Brasil, Instituto de Pesquisas Biomédicas, Hospital Naval Marcilio Dias, Rio de Janeiro, Rio de Janeiro, BrazilNúcleo de Enfrentamento e Estudos de Doenças Infecciosas Emergentes e Reemergentes (NEEDIER), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilMarinha do Brasil, Instituto de Pesquisas Biomédicas, Hospital Naval Marcilio Dias, Rio de Janeiro, Rio de Janeiro, BrazilNúcleo de Enfrentamento e Estudos de Doenças Infecciosas Emergentes e Reemergentes (NEEDIER), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilMarinha do Brasil, Instituto de Pesquisas Biomédicas, Hospital Naval Marcilio Dias, Rio de Janeiro, Rio de Janeiro, BrazilHospital das Clínicas, (HC-UFMG/EBSERH), Belo Horizonte, MG, Brazil, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartamento de genética, Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilNúcleo de Enfrentamento e Estudos de Doenças Infecciosas Emergentes e Reemergentes (NEEDIER), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de genética, Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartamento de genética, ecologia e evolução, Laboratório de biologia integrativa, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartamento de genética, Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de genética, ecologia e evolução, Laboratório de biologia integrativa, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilBackground 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 ACE1 may influence ACE2 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 (n = 134) and Rio de Janeiro (n = 41). A swab of mild patients in Rio de Janeiro who were not hospitalized (n = 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. ACE1, ACE2, TMPRSS2, and B2M (reference gene) expression levels were evaluated in 40 cycles of quantitative PCR. ACE1 Alu 287 bp polymorphism was genotyped using the FastStart Universal SYBR Green Master kit. Results The median age differed between clinical sites (p = 0.016), but no difference in median days of hospitalization was observed (p = 0.329). Age was associated with severity (p = 0.014) and mortality (p = 0.014) in the Belo Horizonte cohort. No alteration in ACE1, ACE2 and TMPRSS2 expression was associated with severity or mortality. ACE1 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]).https://peerj.com/articles/18508.pdfMolecular epidemiologyIndelGenetic associationGenetic variabilityBiomarkers |
| spellingShingle | João Locke Ferreira de Araújo Átila Duque Rossi Jessica Maciel de Almeida Hugo José Alves Isabela de Carvalho Leitão Renata Eliane de Ávila Anna Carla Pinto Castiñeiras Jéssica da Silva Oliveira Rafael Mello Galliez Marlon Daniel Lima Tonini Débora Souza Faffe Shana Priscila Coutinho Barroso Barroso Gustavo Gomes Resende Cássia Cristina Alves Gonçalves Terezinha Marta Pereira Pinto Castiñeiras Amilcar Tanuri Mauro Martins Teixeira Renato Santana Aguiar Cynthia Chester Cardoso Renan Pedra de Souza Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients PeerJ Molecular epidemiology Indel Genetic association Genetic variability Biomarkers |
| title | Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients |
| title_full | Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients |
| title_fullStr | Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients |
| title_full_unstemmed | Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients |
| title_short | Genetic determinants of COVID-19 severity and mortality: ACE1 Alu 287 bp polymorphism and ACE1, ACE2, TMPRSS2 expression in hospitalized patients |
| title_sort | genetic determinants of covid 19 severity and mortality ace1 alu 287 bp polymorphism and ace1 ace2 tmprss2 expression in hospitalized patients |
| topic | Molecular epidemiology Indel Genetic association Genetic variability Biomarkers |
| url | https://peerj.com/articles/18508.pdf |
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