Key result
Four missense mutations in the hACE2 gene showed significant minor allele frequency differences between Asians and Caucasians, with two variants potentially affecting SARS-CoV-2 S protein binding.
Why the study?
Regional variations exist in COVID-19 susceptibility and severity, but there is a paucity of data regarding differences in ACE2 polymorphisms and expression levels between ethnicities.
Observational
Subtle genetic variations in the hACE2 receptor exist between European and East Asian populations, which may theoretically influence SARS-CoV-2 binding, though clinical significance remains unclear.
Answers are grounded in this paper and cite their sources.
hACE2 variants differing by ancestry may influence SARS-CoV-2 binding; leaves open clinical relevance and requires functional validation.
BACKGROUND: There appears to be large regional variation for susceptibility, severity, and mortality for COVID-19 infections. Numerous potential factors could explain the wide variability in the number of infections and death among the countries. We examined genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS-CoV-2. At present, there is a paucity of data regarding the differences for ACE2 polymorphisms and expression levels between ethnicities. METHODS: We compared the allele frequency of mutations between European and East Asians. Molecular dynamic simulation were performed to investigate the influences of significant mutant on protein structure. The binding free energies were calculated between S protein and hACE2. We also examined hACE2 gene expression in eight global populations from HapMap3. RESULTS: Four missense mutations showed significant minor allele frequency difference between Asians and Caucasians. Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. We also noted marginal differences in gene expression for some populations in HapMap3 as compared to the Chinese population. CONCLUSION: Our studies reveal subtle changes in the genetics of hACE2 between human populations, but the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies.
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Li et al. (2020) conducted an observational in COVID-19. hACE2 gene polymorphisms and expression levels vs. Different ethnic populations (e.g., European vs East Asians) was evaluated on Allele frequency of mutations and hACE2 gene expression. Four missense mutations in the hACE2 gene showed significant minor allele frequency differences between Asians and Caucasians, with two variants potentially affecting SARS-CoV-2 S protein binding.
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