PMID- 32558308
OWN - NLM
STAT- MEDLINE
DCOM- 20200826
LR  - 20240329
IS  - 2324-9269 (Electronic)
IS  - 2324-9269 (Linking)
VI  - 8
IP  - 8
DP  - 2020 Aug
TI  - Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among 
      various ethnic populations.
PG  - e1344
LID - 10.1002/mgg3.1344 [doi]
LID - e1344
AB  - 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.
CI  - (c) 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley 
      Periodicals LLC.
FAU - Li, Quan
AU  - Li Q
AD  - Department of Medicine, Faculty of Medicine, Memorial University, St. John's, NL, 
      Canada.
AD  - Princess Margaret Cancer Centre, University Health Network, University of 
      Toronto, Toronto, ON, Canada.
FAU - Cao, Zanxia
AU  - Cao Z
AD  - Shandong Provincial Key Laboratory of Biophysics, Institute of Biophysics, Dezhou 
      University, Dezhou, China.
FAU - Rahman, Proton
AU  - Rahman P
AUID- ORCID: 0000-0002-4521-2029
AD  - Department of Medicine, Faculty of Medicine, Memorial University, St. John's, NL, 
      Canada.
LA  - eng
GR  - 781-19095-209843/Atlantic Canada Opportunities Agency/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200618
PL  - United States
TA  - Mol Genet Genomic Med
JT  - Molecular genetics & genomic medicine
JID - 101603758
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.17.23 (ACE2 protein, human)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - Angiotensin-Converting Enzyme 2
MH  - Asian People/genetics
MH  - Betacoronavirus/isolation & purification/metabolism
MH  - Binding Sites
MH  - COVID-19
MH  - Coronavirus Infections/pathology/virology
MH  - Gene Frequency
MH  - Humans
MH  - Molecular Dynamics Simulation
MH  - Mutation, Missense
MH  - Pandemics
MH  - Peptidyl-Dipeptidase A/chemistry/*genetics/metabolism
MH  - Pneumonia, Viral/pathology/virology
MH  - *Polymorphism, Genetic
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - SARS-CoV-2
MH  - Spike Glycoprotein, Coronavirus/chemistry/metabolism
MH  - White People/genetics
PMC - PMC7323111
OTO - NOTNLM
OT  - COVID-19
OT  - SARS-CoV-2
OT  - angiotensin-converting enzyme 2
OT  - ethnic variation
OT  - gene expression
OT  - molecular dynamics simulation
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/06/20 06:00
MHDA- 2020/08/28 06:00
PMCR- 2020/06/18
CRDT- 2020/06/20 06:00
PHST- 2020/04/15 00:00 [received]
PHST- 2020/05/15 00:00 [revised]
PHST- 2020/05/19 00:00 [accepted]
PHST- 2020/06/20 06:00 [pubmed]
PHST- 2020/08/28 06:00 [medline]
PHST- 2020/06/20 06:00 [entrez]
PHST- 2020/06/18 00:00 [pmc-release]
AID - MGG31344 [pii]
AID - 10.1002/mgg3.1344 [doi]
PST - ppublish
SO  - Mol Genet Genomic Med. 2020 Aug;8(8):e1344. doi: 10.1002/mgg3.1344. Epub 2020 Jun 
      18.