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A survey of genetic variants in SARS-CoV-2 interacting domains of ACE2, TMPRSS2 and TLR3/7/8 across populations.
Lee, In-Hee; Lee, Ji-Won; Kong, Sek Won.
  • Lee IH; Computational Health Informatics Program, Boston Children's Hospital, Boston, MA 02115, USA.
  • Lee JW; Department of Nephrology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pharmacology, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8549, Japan.
  • Kong SW; Computational Health Informatics Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: sekwon.kong@childrens.harvard.edu.
Infect Genet Evol ; 85: 104507, 2020 11.
Article in English | MEDLINE | ID: covidwho-731865
ABSTRACT
The COVID-19 pandemic highlighted healthcare disparities in multiple countries. As such morbidity and mortality vary significantly around the globe between populations and ethnic groups. Underlying medical conditions and environmental factors contribute higher incidence in some populations and a genetic predisposition may play a role for severe cases with respiratory failure. Here we investigated whether genetic variation in the key genes for viral entry to host cells-ACE2 and TMPRSS2-and sensing of viral genomic RNAs (i.e., TLR3/7/8) could explain the variation in incidence across diverse ethnic groups. Overall, these genes are under strong selection pressure and have very few nonsynonymous variants in all populations. Genetic determinant for the binding affinity between SARS-CoV-2 and ACE2 does not show significant difference between populations. Non-genetic factors are likely to contribute differential population characteristics affected by COVID-19. Nonetheless, a systematic mutagenesis study on the receptor binding domain of ACE2 is required to understand the difference in host-viral interaction across populations.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Toll-Like Receptors / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Experimental Studies / Observational study / Randomized controlled trials / Systematic review/Meta Analysis Topics: Variants Limits: Humans Language: English Journal: Infect Genet Evol Journal subject: Biology / Communicable Diseases / Genetics Year: 2020 Document Type: Article Affiliation country: J.meegid.2020.104507

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases / Toll-Like Receptors / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 Type of study: Experimental Studies / Observational study / Randomized controlled trials / Systematic review/Meta Analysis Topics: Variants Limits: Humans Language: English Journal: Infect Genet Evol Journal subject: Biology / Communicable Diseases / Genetics Year: 2020 Document Type: Article Affiliation country: J.meegid.2020.104507