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http://dx.doi.org/10.14348/molcells.2021.2249

Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates  

Jeon, Sungwon (Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST))
Blazyte, Asta (Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST))
Yoon, Changhan (Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST))
Ryu, Hyojung (Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST))
Jeon, Yeonsu (Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST))
Bhak, Youngjune (Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST))
Bolser, Dan (Geromics, Ltd.)
Manica, Andrea (Department of Zoology, University of Cambridge)
Shin, Eun-Seok (Division of Cardiology, Department of Internal Medicine, Ulsan Medical Center)
Cho, Yun Sung (Clinomics, Inc.)
Kim, Byung Chul (Clinomics, Inc.)
Ryoo, Namhee (Department of Laboratory Medicine, Keimyung University School of Medicine)
Choi, Hansol (Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST))
Bhak, Jong (Korean Genomics Center (KOGIC), Ulsan National Institute of Science and Technology (UNIST))
Publication Information
Molecules and Cells / v.44, no.9, 2021 , pp. 680-687 More about this Journal
Abstract
Coronavirus disease, COVID-19 (coronavirus disease 2019), caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has a higher case fatality rate in European countries than in others, especially East Asian ones. One potential explanation for this regional difference is the diversity of the viral infection efficiency. Here, we analyzed the allele frequencies of a nonsynonymous variant rs12329760 (V197M) in the TMPRSS2 gene, a key enzyme essential for viral infection and found a significant association between the COVID-19 case fatality rate and the V197M allele frequencies, using over 200,000 present-day and ancient genomic samples. East Asian countries have higher V197M allele frequencies than other regions, including European countries which correlates to their lower case fatality rates. Structural and energy calculation analysis of the V197M amino acid change showed that it destabilizes the TMPRSS2 protein, possibly negatively affecting its ACE2 and viral spike protein processing.
Keywords
allele frequency; case fatality rate; COVID-19; SARS-CoV-2; TMPRSS2;
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