SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study

Abstract The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genet...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hossein Lanjanian, Maryam Moazzam-Jazi, Mehdi Hedayati, Mahdi Akbarzadeh, Kamran Guity, Bahareh Sedaghati-khayat, Fereidoun Azizi, Maryam S. Daneshpour
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/21b3d7a2df49435a8a07c4ea87883957
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:21b3d7a2df49435a8a07c4ea87883957
record_format	dspace
spelling	oai:doaj.org-article:21b3d7a2df49435a8a07c4ea878839572021-12-02T14:01:33ZSARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study10.1038/s41598-020-80325-x2045-2322https://doaj.org/article/21b3d7a2df49435a8a07c4ea878839572021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80325-xhttps://doaj.org/toc/2045-2322Abstract The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.Hossein LanjanianMaryam Moazzam-JaziMehdi HedayatiMahdi AkbarzadehKamran GuityBahareh Sedaghati-khayatFereidoun AziziMaryam S. DaneshpourNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hossein Lanjanian Maryam Moazzam-Jazi Mehdi Hedayati Mahdi Akbarzadeh Kamran Guity Bahareh Sedaghati-khayat Fereidoun Azizi Maryam S. Daneshpour SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
description	Abstract The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.
format	article
author	Hossein Lanjanian Maryam Moazzam-Jazi Mehdi Hedayati Mahdi Akbarzadeh Kamran Guity Bahareh Sedaghati-khayat Fereidoun Azizi Maryam S. Daneshpour
author_facet	Hossein Lanjanian Maryam Moazzam-Jazi Mehdi Hedayati Mahdi Akbarzadeh Kamran Guity Bahareh Sedaghati-khayat Fereidoun Azizi Maryam S. Daneshpour
author_sort	Hossein Lanjanian
title	SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
title_short	SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
title_full	SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
title_fullStr	SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
title_full_unstemmed	SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study
title_sort	sars-cov-2 infection susceptibility influenced by ace2 genetic polymorphisms: insights from tehran cardio-metabolic genetic study
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/21b3d7a2df49435a8a07c4ea87883957
work_keys_str_mv	AT hosseinlanjanian sarscov2infectionsusceptibilityinfluencedbyace2geneticpolymorphismsinsightsfromtehrancardiometabolicgeneticstudy AT maryammoazzamjazi sarscov2infectionsusceptibilityinfluencedbyace2geneticpolymorphismsinsightsfromtehrancardiometabolicgeneticstudy AT mehdihedayati sarscov2infectionsusceptibilityinfluencedbyace2geneticpolymorphismsinsightsfromtehrancardiometabolicgeneticstudy AT mahdiakbarzadeh sarscov2infectionsusceptibilityinfluencedbyace2geneticpolymorphismsinsightsfromtehrancardiometabolicgeneticstudy AT kamranguity sarscov2infectionsusceptibilityinfluencedbyace2geneticpolymorphismsinsightsfromtehrancardiometabolicgeneticstudy AT baharehsedaghatikhayat sarscov2infectionsusceptibilityinfluencedbyace2geneticpolymorphismsinsightsfromtehrancardiometabolicgeneticstudy AT fereidounazizi sarscov2infectionsusceptibilityinfluencedbyace2geneticpolymorphismsinsightsfromtehrancardiometabolicgeneticstudy AT maryamsdaneshpour sarscov2infectionsusceptibilityinfluencedbyace2geneticpolymorphismsinsightsfromtehrancardiometabolicgeneticstudy
_version_	1718392127542525952

SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study

Ejemplares similares