Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates
Regional TMPRSS2 V197M Allele Frequencies Are Correlated with COVID-19 Case Fatality Rates
전성원(울산과학기술원); Asta Blazyte(울산과학기술원); 윤창한(울산과학기술원); 류효정(UNIST); Yeonsu Jeon(UNIST); 박영준(울산과학기술원 게놈산업기술센터); Dan Bolser(Geromics, Ltd.); Andrea Manica(University of Cambridge); Eun-Seok Shin(Ulsan Medical Center); Yun Sung Cho(Clinomics, Inc.); 김병철(Clinomics, Inc.); Namhee Ryoo(Keimyung University); 최한솔(UNIST); Jong Bhak(Ulsan National Institute of Science and Technology)
44권 9호, 680~687쪽
초록
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.
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.
- 발행기관:
- 한국분자세포생물학회
- 분류:
- 생물학