Variation in genes associated with viral entry of SARS-CoV-2 unlikely to influence COVID-19 morbidity and mortality, study finds

Date:
September 24, 2020
Source:
Hokkaido University
Summary:
A comprehensive search of genetic variation databases has revealed
no significant differences across populations and ethnic groups
in seven genes associated with viral entry of SARS-CoV-2.



FULL STORY ==========================================================================
A comprehensive search of genetic variation databases has revealed no significant differences across populations and ethnic groups in seven
genes associated with viral entry of SARS-CoV-2.


========================================================================== African Americans and Latinos in the United States and ethnic minorities
in the United Kingdom are disproportionately affected by COVID-19. They
are more likely to develop severe symptoms and also show significantly
higher mortality compared with other regional and ethnic groups.

To investigate if this disparity could be caused by genetic variation,
a team of three researchers -- including Assistant Professor Ji-Won Lee
of Hokkaido University's Graduate School of Dental Medicine -- surveyed publicly available databases of genomic variants, including gnomAD, the
Korean Reference Genome Database, TogoVar (a Japanese genetic variation database) and the 1000 Genomes Project. They studied variants across
multiple regional and ethnic groups in seven genes known to play roles
in viral entry into host cells and recognition of viral RNA in host cells.

SARS-CoV-2 has spiked protein (S protein) on its envelope, which encloses
the virus. Before the virus can enter host cells, the S protein has
to bind with the ACE2 receptor on the cell surface. It is then broken
into two pieces by the enzymes TMPRSS2 and cathepsin B and L. After the
virus enters the cells, the viral RNA binds with proteins such as TLR3,
TLR7 and TLR8, triggering an innate immune response.

According to the results, there were genetic variants in these seven
proteins, with the largest number of variants in ACE2. However, very
few of these variations alter the functions of these proteins. Since the overall variation frequency was extremely low (less than 0.01 percent),
the scientists determined there is no significant difference across
populations or ethnic groups in the functions of the seven proteins
involved in infection.

The team's findings suggest that differences in morbidity and mortality
are not the result of genetic variations in genes for viral entry across populations.

Rather, it is more likely that preexisting medical conditions, individual medical histories, environmental factors and healthcare disparities
play a significant role in affecting the morbidity and mortality of
COVID-19. However, due to the limited size of the population databases
used in this study, additional research using more diverse human genome databases is required.

Additionally, other studies have shown that genetic factors may contribute
to serious cases.

Also taking part in the study were In-Hee Lee of Boston Children's
Hospital (Computational Health Informatics Program) and Sek Won Kong of
Harvard Medical School (Department of Pediatrics). The team's findings
were published online on August 25, 2020, in the medical journal
Infection, Genetics and Evolution.


========================================================================== Story Source: Materials provided by Hokkaido_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. In-Hee Lee, Ji-Won Lee, Sek Won Kong. A survey of genetic
variants in
SARS-CoV-2 interacting domains of ACE2, TMPRSS2 and TLR3/7/8
across populations. Infection, Genetics and Evolution, 2020; 85:
104507 DOI: 10.1016/j.meegid.2020.104507 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200924114007.htm

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