A Systematic Review on Association of ACE2 and/or TMPRSS2 Polymorphism with Susceptibility to SARS-CoV-2 Infections

Hasnul Hadi, Nurul Husna (2021) A Systematic Review on Association of ACE2 and/or TMPRSS2 Polymorphism with Susceptibility to SARS-CoV-2 Infections. [Project Paper] (Submitted)

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). It infects the human cells through binding of subunit 1 of the coronavirus spike (S) protein with the angiotensinconverting enzyme 2 (ACE2) receptor and is activated by transmembrane serine protease 2 (TMPRSS2) through cleavage of the S protein at subunit 2 for fusion with the human cell membrane. Polymorphism is a condition where there are variations in the DNA sequences of an individual which determine the diversity of individuals, groups and populations. These polymorphisms could have an effect on the susceptibility and severity of a disease in individuals. Although there are numerous studies that state the importance of ACE2 and TMPRSS2 in SARS-CoV-2 infection, studies that relate polymorphism of both transmembrane proteins to susceptibility to SARS-CoV-2 infections are still lacking. Objective: This systematic study aims to investigate the susceptibility to SARS-CoV-2 infections in individuals with ACE2 and/or TMPRSS2 polymorphisms. Methodology: Studies related to ACE2, TMPRSS2 and COVID-19 identified from four databases - Scopus, ScienceDirect,PubMed and EBSCOhost that fit the pre-defined criteria underwent initial and fulltext screening. A total of seven studies were then subjected to systematic review. Results: Systematic review determining the association of ACE2 and/or TMPRSS2 polymorphism with susceptibility to SARS-CoV-2 infections revealed ambiguous results in the studied population. There was no association observed between the ACE2 polymorphism and susceptibility to SARS-CoV-2 infections. Meanwhile, some of TMPRSS2 variants such as rs7282236, rs75603675 and rs61735789 were associated with COVID-19 test positivity and some other TMPRSS2 variants such as rs12329760, rs200291871, rs61735792 and rs61735794 might be linked with SARSCoV- 2 infections. Discussion: There are several factors such as the type and the location of the polymorphism which were found to affect the susceptibility to SARSCoV- 2 infections. Some of the polymorphisms found in the studies were single nucleotide polymorphism (SNP), silent or synonymous polymorphism, missense, intronic and mixture of insertion and deletion (indels). ACE2 polymorphisms were commonly found in the control group compared to the patients. It is determined that ACE2 polymorphisms of all types and locations were not found to affect the susceptibility to infections but it may affect the severity of diseases in the patients. As for TMPRSS2 polymorphisms, it was frequently found in the COVID-19 patients and most of the variants found were linked to SARS-CoV-2 infections regardless of the types of polymorphism. Conclusion: This systematic review reveals mixed findings on the association of ACE2 and/or TMPRSS2 polymorphism with the susceptibility to SARS-CoV-2 infection. Generally, the findings are mostly from small populations and therefore not sufficient to conclude the association of ACE2 and/or TMPRSS2 polymorphism with susceptibility to SARS-CoV-2 infection. There is a need for these studies to be done in a larger population to better understand the possible association of both proteins to SARS-CoV-2 infections.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	22 Aug 2023 07:44
Last Modified:	22 Aug 2023 07:44
URI:	http://psaspb.upm.edu.my/id/eprint/1041

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