Bioinformatics Analysis of Allele Frequencies and Expression Patterns of ACE2, TMPRSS2 and FURIN in Different Populations and Susceptibility to SARS-CoV-2.

Mohammad Tarek,Anwar Abdelnaser,Hassan A N El-Fawal,Mohammed M Salama,Firas Kobeissy,Hana Abdelzaher

doi:10.3390/genes12071041

Abstract

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2’s receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN’s potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.

Highlights

IntroductionIn February 2020, the most recent addition to the coronavirus family (severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2 in short) was already taking the world by storm
In February 2020, the most recent addition to the coronavirus family was already taking the world by storm
We concluded that the characteristic patterns of expression of FURIN, angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 might provide important insights into the dynamics of SARS-CoV-2 infection

Summary

Introduction

In February 2020, the most recent addition to the coronavirus family (severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2 in short) was already taking the world by storm It was spreading at such a rapid rate that the WHO made the announcement that the virus and its associated pneumonia were a pandemic public health menace [1]. With the current ambiguity surrounding trends in SARS-CoV-2 infectivity, there is a dire need for attempts to gain insights into the mechanisms governing this infection. Evidence suggests that this variation in population infectivity and severity may be accounted for by expression quantitative trait loci (eQTL) (genetic loci explaining part of the variations of gene expression phenotypes) and differences in their frequencies [5]. EQTLs are identified through genome-wide association studies (GWAS), which analyze associations between genetic variation markers and gene expression levels in large cohorts of individuals [6]

Objectives

Methods

Results

Discussion

Conclusion