Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic, with an alarming infectivity and mortality rate. Studies have examined genetic effects on SARS-CoV-2 disease susceptibility and severity within Eurasian populations. These studies identified contrasting effects on the severity of disease between African populations. Genetic factors can explain some of the diversity observed within SARS-CoV-2 disease susceptibility and severity. Single nucleotide polymorphisms (SNPs) within the SARS-CoV-2 receptor genes have demonstrated detrimental and protective effects across ethnic groups. For example, the TT genotype of rs2285666 (Angiotensin-converting enzyme 2 (ACE2)) is associated with the severity of SARS-CoV-2 disease, which is found at higher frequency within Asian individuals compared to African and European individuals. In this study, we examined four SARS-CoV-2 receptors, ACE2, Transmembrane serine protease 2 (TMPRSS2), Neuropilin-1 (NRP1), and Basigin (CD147). A total of 42 SNPs located within the four receptors were reviewed: ACE2 (12), TMPRSS2 (10), BSG (CD147) (5), and NRP1 (15). These SNPs may be determining factors for the decreased disease severity observed within African individuals. Furthermore, we highlight the absence of genetic studies within the African population and emphasize the importance of further research. This review provides a comprehensive summary of specific variants within the SARS-CoV-2 receptor genes, which can offer a better understanding of the pathology of the SARS-CoV-2 pandemic and identify novel potential therapeutic targets.

Keywords: ACE2; CD147; COVID-19; NRP1; SARS-CoV-2; SNP; TMPRSS2.

Figure 1

Polymorphisms within ACE2 (rs2285666), TMPRSS2 (rs12329760), NRP1 (rs10080), and CD147 (rs8259) contribute to variability in SARS-CoV-2 viral load. (A) Specific alleles facilitate viral entry and, thus, increased viral load, (B) while others disrupt protein function and reduce viral entry into the cell, resulting in lower viral load.

Figure 2

Inclusion and exclusion criteria used to select SNPs discussed in this review for SARS-CoV-2 receptors and co-receptors ACE2, TMPRSS2, NRP1, and BSG(CD147) genes.