Genetic variation unlikely to affect COVID-19 morbidity and mortality

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Genetic variation unlikely to influence COVID-19 morbidity and mortality

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A comprehensive search of genetic variation databases did not reveal any significant differences between populations and ethnic groups in seven genes associated with viral onset of SARS-CoV-2.

African Americans and Latinos in the US, as well as ethnic minorities in the UK, are disproportionately affected by COVID-19. They are more likely to develop severe symptoms and have significantly higher mortality rates compared to other regional and ethnic groups.

To investigate whether this inequality could be caused by genetic variation, a team of three researchers – including Assistant Professor Ji-Won Lee of the Graduate School of Dentistry at Hokkaido University – examined publicly available genomic variant databases, including gnomAD, the Korean reference genome database , TogoVar (a Japanese genetic variation database) and the 1000 Genome Project. They examined variants across multiple regional and ethnic groups in seven genes known to play a role in the entry of viruses into host cells and in the recognition of viral RNA in host cells.

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

The results showed that there were genetic variants in these seven proteins, with most of the variants being present in ACE2. However, very few of these variations change the functions of these proteins. Because the overall frequency of variation was extremely low (less than 0.01 percent), the scientists found that there was no significant difference between populations or ethnic groups in the functions of the seven proteins involved in the infection.

The team's results suggest that differences in morbidity and mortality are not due to genetic variations in the genes for virus entry in different populations. Rather, it is more likely that pre-existing medical conditions, individual medical histories, environmental factors, and healthcare differences play important roles in influencing the morbidity and mortality of COVID-19. However, due to the limited size of the population databases used in this study, additional studies using more diverse human genome databases are required. In addition, other studies have shown that genetic factors can contribute to serious cases.

The researchers identify genetic factors that can influence susceptibility to COVID-19

More information:
In-Hee Lee et al. An investigation of genetic variants in SARS-CoV-2 interacting domains of ACE2, TMPRSS2 and TLR3 / 7/8 across populations, infections, genetics and evolution (2020). DOI: 10.1016 / j.meegid.2020.104507

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Hokkaido University

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Genetic Variation Unlikely to Affect COVID-19 Morbidity and Mortality (2020, Sep 24)
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