Cargando…

Genetic analysis of ACE2 peptidase domain in SARS-CoV-2-positive and SARS-CoV-2-negative individuals from Pakistan

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has emerged as a serious public health emergency of global concern. Angiotensin converting enzyme 2 (ACE2) peptidase domain is important for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Germline va...

Descripción completa

Detalles Bibliográficos
Autores principales: Muhammad, Noor, Naeemi, Humaira, Azeem, Ayesha, Sadaqat, Rida, Shehzad, Umara, Siddique, Kashif, Hassan, Usman, Raza, Aun, Rashid, Muhammad Usman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10016156/
https://www.ncbi.nlm.nih.gov/pubmed/36920597
http://dx.doi.org/10.1007/s11033-023-08315-6
_version_ 1784907346443501568
author Muhammad, Noor
Naeemi, Humaira
Azeem, Ayesha
Sadaqat, Rida
Shehzad, Umara
Siddique, Kashif
Hassan, Usman
Raza, Aun
Rashid, Muhammad Usman
author_facet Muhammad, Noor
Naeemi, Humaira
Azeem, Ayesha
Sadaqat, Rida
Shehzad, Umara
Siddique, Kashif
Hassan, Usman
Raza, Aun
Rashid, Muhammad Usman
author_sort Muhammad, Noor
collection PubMed
description BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has emerged as a serious public health emergency of global concern. Angiotensin converting enzyme 2 (ACE2) peptidase domain is important for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Germline variants in ACE2 peptidase domain may influence the susceptibility for SARS-CoV-2 infection and disease severity in the host population. ACE2 genetic analysis among Caucasians showed inconclusive results. This is the first Asian study investigating the contribution of ACE2 germline variants to SARS-CoV-2 infection in Pakistani population. METHODS: In total, 442 individuals, including SARS-CoV-2-positive (n = 225) and SARS-CoV-2-negative (n = 217) were screened for germline variants in ACE2 peptidase domain (exons 2, 3, 9, and 10) using high resolution melting and denaturing high-performance liquid chromatography analyses followed by DNA sequencing of variant fragments. The identified variant was analyzed by in silico tools for potential effect on ACE2 protein. RESULTS: A missense variant, p.Lys26Arg, was identified in one SARS-CoV-2-positive (1/225; 0.4%) and three SARS-CoV-2-negative (3/217; 1.4%) individuals. No significant difference in the minor allele frequency of this variant was found among SARS-CoV-2-positive and SARS-CoV-2-negative individuals (1/313; 0.3% versus 3/328; 0.9%; P = 0.624), respectively. The SARS-CoV-2-positive patient carrying p.Lys26Arg showed mild COVID-19 disease symptoms. It was predicted as benign variant by in silico tool. No variant was detected in ACE2 residues important for binding of SARS-CoV-2 spike protein. CONCLUSION: The p.Lys26Arg variant may have no association with SARS-CoV-2 susceptibility in Pakistani population. Whole ACE2 gene screening is warranted to clarify its role in SARS-CoV-2 infection.
format Online
Article
Text
id pubmed-10016156
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Springer Netherlands
record_format MEDLINE/PubMed
spelling pubmed-100161562023-03-15 Genetic analysis of ACE2 peptidase domain in SARS-CoV-2-positive and SARS-CoV-2-negative individuals from Pakistan Muhammad, Noor Naeemi, Humaira Azeem, Ayesha Sadaqat, Rida Shehzad, Umara Siddique, Kashif Hassan, Usman Raza, Aun Rashid, Muhammad Usman Mol Biol Rep Original Article BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has emerged as a serious public health emergency of global concern. Angiotensin converting enzyme 2 (ACE2) peptidase domain is important for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Germline variants in ACE2 peptidase domain may influence the susceptibility for SARS-CoV-2 infection and disease severity in the host population. ACE2 genetic analysis among Caucasians showed inconclusive results. This is the first Asian study investigating the contribution of ACE2 germline variants to SARS-CoV-2 infection in Pakistani population. METHODS: In total, 442 individuals, including SARS-CoV-2-positive (n = 225) and SARS-CoV-2-negative (n = 217) were screened for germline variants in ACE2 peptidase domain (exons 2, 3, 9, and 10) using high resolution melting and denaturing high-performance liquid chromatography analyses followed by DNA sequencing of variant fragments. The identified variant was analyzed by in silico tools for potential effect on ACE2 protein. RESULTS: A missense variant, p.Lys26Arg, was identified in one SARS-CoV-2-positive (1/225; 0.4%) and three SARS-CoV-2-negative (3/217; 1.4%) individuals. No significant difference in the minor allele frequency of this variant was found among SARS-CoV-2-positive and SARS-CoV-2-negative individuals (1/313; 0.3% versus 3/328; 0.9%; P = 0.624), respectively. The SARS-CoV-2-positive patient carrying p.Lys26Arg showed mild COVID-19 disease symptoms. It was predicted as benign variant by in silico tool. No variant was detected in ACE2 residues important for binding of SARS-CoV-2 spike protein. CONCLUSION: The p.Lys26Arg variant may have no association with SARS-CoV-2 susceptibility in Pakistani population. Whole ACE2 gene screening is warranted to clarify its role in SARS-CoV-2 infection. Springer Netherlands 2023-03-15 2023 /pmc/articles/PMC10016156/ /pubmed/36920597 http://dx.doi.org/10.1007/s11033-023-08315-6 Text en © The Author(s), under exclusive licence to Springer Nature B.V. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Article
Muhammad, Noor
Naeemi, Humaira
Azeem, Ayesha
Sadaqat, Rida
Shehzad, Umara
Siddique, Kashif
Hassan, Usman
Raza, Aun
Rashid, Muhammad Usman
Genetic analysis of ACE2 peptidase domain in SARS-CoV-2-positive and SARS-CoV-2-negative individuals from Pakistan
title Genetic analysis of ACE2 peptidase domain in SARS-CoV-2-positive and SARS-CoV-2-negative individuals from Pakistan
title_full Genetic analysis of ACE2 peptidase domain in SARS-CoV-2-positive and SARS-CoV-2-negative individuals from Pakistan
title_fullStr Genetic analysis of ACE2 peptidase domain in SARS-CoV-2-positive and SARS-CoV-2-negative individuals from Pakistan
title_full_unstemmed Genetic analysis of ACE2 peptidase domain in SARS-CoV-2-positive and SARS-CoV-2-negative individuals from Pakistan
title_short Genetic analysis of ACE2 peptidase domain in SARS-CoV-2-positive and SARS-CoV-2-negative individuals from Pakistan
title_sort genetic analysis of ace2 peptidase domain in sars-cov-2-positive and sars-cov-2-negative individuals from pakistan
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10016156/
https://www.ncbi.nlm.nih.gov/pubmed/36920597
http://dx.doi.org/10.1007/s11033-023-08315-6
work_keys_str_mv AT muhammadnoor geneticanalysisoface2peptidasedomaininsarscov2positiveandsarscov2negativeindividualsfrompakistan
AT naeemihumaira geneticanalysisoface2peptidasedomaininsarscov2positiveandsarscov2negativeindividualsfrompakistan
AT azeemayesha geneticanalysisoface2peptidasedomaininsarscov2positiveandsarscov2negativeindividualsfrompakistan
AT sadaqatrida geneticanalysisoface2peptidasedomaininsarscov2positiveandsarscov2negativeindividualsfrompakistan
AT shehzadumara geneticanalysisoface2peptidasedomaininsarscov2positiveandsarscov2negativeindividualsfrompakistan
AT siddiquekashif geneticanalysisoface2peptidasedomaininsarscov2positiveandsarscov2negativeindividualsfrompakistan
AT hassanusman geneticanalysisoface2peptidasedomaininsarscov2positiveandsarscov2negativeindividualsfrompakistan
AT razaaun geneticanalysisoface2peptidasedomaininsarscov2positiveandsarscov2negativeindividualsfrompakistan
AT rashidmuhammadusman geneticanalysisoface2peptidasedomaininsarscov2positiveandsarscov2negativeindividualsfrompakistan