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

Theolan Adimulam; Thilona Arumugam; Anmol Gokul; Veron Ramsuran

doi:10.3390/ijms24108711

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

Int J Mol Sci. 2023 May 13;24(10):8711. doi: 10.3390/ijms24108711.

Authors

Theolan Adimulam¹, Thilona Arumugam¹, Anmol Gokul¹, Veron Ramsuran^{1

2}

Affiliations

¹ School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa.
² Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban 4041, South Africa.

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.

Publication types

Review

MeSH terms

Angiotensin-Converting Enzyme 2 / genetics
COVID-19* / genetics
Disease Susceptibility
Ethnicity
Humans
SARS-CoV-2* / genetics

Substances

Angiotensin-Converting Enzyme 2

Grants and funding

This publication was supported by the South African Medical Research Council with funds received from the South African Department of Science and Technology. V.R. was funded as a FLAIR Research Fellow (the Future Leader in African Independent Research (FLAIR)) Fellowship Programme was a partnership between the African Academy of Sciences (AAS) and the Royal Society that was funded by the UK Government as part of the Global Challenge Research Fund (GCRF) Grant # FLAIR-FLR\R1\190204]; supported by the South African Medical Research Council (SAMRC) with funds from the Department of Science and Technology (DST); and V.R. was also supported in part through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (Grant # DEL-15-006) by the AAS. This is supported by The South African Medical Research Council through the Self-initiated Research Grant. A.G. is supported by Poliomyelitis Research Foundation (PRF) Bursaries. T.A. (Thilona Arumugam) is funded by South African Medical Research Council Self-Initiated Research Grant and L’ORÉAL UNESCO for Woman in Science South African Young Talent fellow. T.A. (Theolan Adimulam) is funded by the Poliomyelitis Research Foundation (PRF) Bursary.