Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among various ethnic populations

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.

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.

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.

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.