Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among various ethnic populations.
Angiotensin-Converting Enzyme 2
Asian People
/ genetics
Betacoronavirus
/ isolation & purification
Binding Sites
COVID-19
Coronavirus Infections
/ pathology
Gene Frequency
Humans
Molecular Dynamics Simulation
Mutation, Missense
Pandemics
Peptidyl-Dipeptidase A
/ chemistry
Pneumonia, Viral
/ pathology
Polymorphism, Genetic
Protein Binding
Protein Structure, Tertiary
SARS-CoV-2
Spike Glycoprotein, Coronavirus
/ chemistry
White People
/ genetics
COVID-19
SARS-CoV-2
angiotensin-converting enzyme 2
ethnic variation
gene expression
molecular dynamics simulation
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
15
04
2020
revised:
15
05
2020
accepted:
19
05
2020
pubmed:
20
6
2020
medline:
28
8
2020
entrez:
20
6
2020
Statut:
ppublish
Résumé
There appears to be large regional variation for susceptibility, severity, and mortality for COVID-19 infections. Numerous potential factors could explain the wide variability in the number of infections and death among the countries. We examined genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS-CoV-2. At present, there is a paucity of data regarding the differences for ACE2 polymorphisms and expression levels between ethnicities. We compared the allele frequency of mutations between European and East Asians. Molecular dynamic simulation were performed to investigate the influences of significant mutant on protein structure. The binding free energies were calculated between S protein and hACE2. We also examined hACE2 gene expression in eight global populations from HapMap3. Four missense mutations showed significant minor allele frequency difference between Asians and Caucasians. Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. We also noted marginal differences in gene expression for some populations in HapMap3 as compared to the Chinese population. Our studies reveal subtle changes in the genetics of hACE2 between human populations, but the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies.
Sections du résumé
BACKGROUND
There appears to be large regional variation for susceptibility, severity, and mortality for COVID-19 infections. Numerous potential factors could explain the wide variability in the number of infections and death among the countries. We examined genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS-CoV-2. At present, there is a paucity of data regarding the differences for ACE2 polymorphisms and expression levels between ethnicities.
METHODS
We compared the allele frequency of mutations between European and East Asians. Molecular dynamic simulation were performed to investigate the influences of significant mutant on protein structure. The binding free energies were calculated between S protein and hACE2. We also examined hACE2 gene expression in eight global populations from HapMap3.
RESULTS
Four missense mutations showed significant minor allele frequency difference between Asians and Caucasians. Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. We also noted marginal differences in gene expression for some populations in HapMap3 as compared to the Chinese population.
CONCLUSION
Our studies reveal subtle changes in the genetics of hACE2 between human populations, but the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies.
Identifiants
pubmed: 32558308
doi: 10.1002/mgg3.1344
pmc: PMC7323111
doi:
Substances chimiques
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Peptidyl-Dipeptidase A
EC 3.4.15.1
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1344Subventions
Organisme : Atlantic Canada Opportunities Agency
ID : 781-19095-209843
Pays : International
Informations de copyright
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
Références
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
PLoS Genet. 2012;8(4):e1002639
pubmed: 22532805
Clin Sci (Lond). 2020 Mar 13;134(5):543-545
pubmed: 32167153
Arch Med Res. 2020 May;51(4):345-346
pubmed: 32279908
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Science. 2020 Mar 27;367(6485):1444-1448
pubmed: 32132184
Nucleic Acids Res. 2007 Jan;35(Database issue):D301-3
pubmed: 17142228
Nat Genet. 2006 Aug;38(8):904-9
pubmed: 16862161
JAMA. 2020 Mar 24;:
pubmed: 32208485
Int J Antimicrob Agents. 2020 Jul;56(1):105949
pubmed: 32205204
Bioinformatics. 2013 Apr 1;29(7):845-54
pubmed: 23407358
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
Nat Rev Microbiol. 2009 Mar;7(3):226-36
pubmed: 19198616
Mol Genet Genomic Med. 2020 Aug;8(8):e1344
pubmed: 32558308
JAMA Intern Med. 2020 Mar 13;:
pubmed: 32167524
Nature. 2010 Apr 1;464(7289):773-7
pubmed: 20220756
J Comput Chem. 2015 Oct 5;36(26):1990-2008
pubmed: 26238484
J Comput Chem. 2019 Oct 15;40(27):2418-2431
pubmed: 31260119
J R Soc Interface. 2012 Dec 12;10(79):20120835
pubmed: 23235262
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651