ACE2, TMPRSS2, and Furin variants and SARS‐CoV‐2 infection in Madrid, Spain

Abstract

It has been suggested that some individuals may present genetic susceptibility to SARS‐CoV‐2 infection, with particular research interest in variants of the ACE2 and TMPRSS2 genes, involved in viral penetration into cells, in different populations and geographic regions, although insufficient information is currently available. This study addresses the apparently reasonable hypothesis that variants of these genes may modulate viral infectivity, making some individuals more vulnerable than others. Through whole‐exome sequencing, the frequency of exonic variants of the ACE2, TMPRSS2 , and Furin genes was analyzed in relation to presence or absence of SARS‐CoV‐2 infection in a familial multiple sclerosis cohort including 120 individuals from Madrid. The ACE2 gene showed a low level of polymorphism, and none variant was significantly associated with SARS‐CoV‐2 infection. These variants have previously been detected in Italy. While TMPRSS2 is highly polymorphic, the variants found do not coincide with those described in other studies, with the exception of rs75603675, which may be associated with SARS‐CoV‐2 infection. The synonymous variants rs61735792 and rs61735794 showed a significant association with infection. Despite the limited number of patients with SARS‐CoV‐2 infection, some variants, especially in TMPRSS2 , may be associated with COVID‐19.

COVID-19 susceptibility: potential of ACE2 polymorphisms

“…This signifies the importance of identifying novel SNPs that can either affect tissue specific ACE2 expression or plasma ACE2 levels. Other studies have also highlighted an association of ACE2 and TMPR SS2 polymorphisms with COVID-19 susceptibility and infection [53,54]. Additionally, coronavirus infection is related to the state of hypercytokinemia/cytokine storm which is characterized by an excessive synthesis of proinflammatory cytokines resulting in severe outcomes that might include multiple organ damage.…”

Interferon-induced transmembrane protein-3 genetic variant rs12252 is associated with COVID-19 mortality

“…The large variability in clinical expression and outcomes of COVID-19 was associated with host factors such as old age, gender, comorbidities, ethnicity, and lower economic status [ 2 , 4 , 6 ]. Emerging studies suggest that host-genetic factors may also contribute to the difference in COVID-19 phenotypes [ [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] ].…”

“…Studies investigating the role of host genetic factors in COVID-19 pathogenesis are rapidly growing, revealing several gene susceptibility variants, although with different levels of evidence [ 7 , 8 , [10] , [11] , [12] , [13] , [14] , [15] ]. Two approaches have been used, including candidate gene [ 7 , 8 , 10 , 11 ] or genome-wide association [ 13 , 15 ].…”

“…Studies investigating the role of host genetic factors in COVID-19 pathogenesis are rapidly growing, revealing several gene susceptibility variants, although with different levels of evidence [ 7 , 8 , [10] , [11] , [12] , [13] , [14] , [15] ]. Two approaches have been used, including candidate gene [ 7 , 8 , 10 , 11 ] or genome-wide association [ 13 , 15 ]. Selected gene candidates included ACE-2 , TMPRSS2 , IFITM3, Toll-like receptor 3 ( TLR3 ), and interferon regulatory factor 7 ( IRF7 ) based on their role in SARS-CoV-2 tropism to the human cells, including binding, entry, and replication as well as host-immune response to the virus [ [7] , [8] , [9] , [10] , [11] , [12] ].…”

An update review of emerging small-molecule therapeutic options for COVID-19

“…The main structural proteins encoded by SARS-CoV-2 include spike (S), membrane (M), envelope (E) and nucleocapsid (N) proteins. The binding of the S protein to host cell receptor angiotensin-converting enzyme 2 (ACE2) [ 5 , 6 ] is the key event for the entry of SARS-CoV-2 into host cells. Furthermore, the binding of the S protein to the cellular transmembrane serine protease (TMPRSS2) might promote the entry of the virus into the host cells.…”