The ACE2 1000 Genome chart, I can only find on Pinterest with no reference. Data making up the chart appears to be from the 1000 Genome database, that is real thing (and highly useful database I use almost daily). I tried searching Google Scholar with the 6 rsid#s numbers mentioned and did not get a single hit for all six appearing together in a paper. That is highly unusual. Normally google scholar returns hundreds to tens of thousands of papers in a keyword search with rsid#s. This search was nada, zilch, zero. These rsid#s indeed represent mutations in the ACE2 gene (that codes for receptor for the nCoV spike protein). These mutations may represent some alteration in how ACE2 is expressed, but no one has systematically studied them as to how they effect the functionality and expression of ACE2 across all populations. This kind of research is what I spend every working day with: and this chart is meaningless in presenting any risk as based on ethnicity and a percentage of people who possess 6 mutations in a gene…….
…..Because: it is very clear from auick review of the literature that there does not exist even a single putative functional variant in ACE2 at this time. Basically that means scientists don’t understand how mutations in this gene effect its activity and/or expressions: either through altered mRNA, deletion of a transcription or repression site, changes to enzyme stability, changes to its catalytic site or Km, etc. In short, mutations effect enzymes in many different ways. The vast majority of mutations to do not effect enzymes at all. At this stage of research, it is more about genome wide association studies (bias eye view of all chromosomes to find areas of interest) to fine mapping of a gene locus (zooming in a gene to look at it alone, not the whole human genome) to start finding what are called “tag” single nucleotide polymorphisms or SNPs, that tag/or are connected to the true underlying functional variant. Even then, there can be more than one functional variant, and understanding how these in combination effect an enzyme is studied through haplotype analysis. The science for this and ACE2 is in its infancy. That Pinterest chart is meaningless in my opinion, as a population frequency chart compliled by adding up alleles from 6 mutations gives you no idea how they are effecting the activity (gain or loss or no change) to an enzyme.
I understand there would be interest in ACE2 mutations given its connection to SARS. Chinese researchers investigated that already after the SARS outbreak and concluded: ACE2 gene polymorphisms do not affect outcome of severe acute respiratory syndrome.https://www.ncbi.nlm.nih.gov/pubmed/15331509
We therefore conclude that although ACE2 serves functionally as the receptor for entry of the SARS coronavirus into human host cells, the evidence provided by this study does not support an association between its common genetic variants and SARS susceptibility or outcome. Despite its X-chromosome location, poor outcomes in male SARS patients do not appear to be related to genetic variants of ACE2.
Chinese researchers did look at other mutations in other genes that might effect susceptibility/severity of SARS and found both negative and positive associations (SNPs that increased risk or seem to offer to offer protection) with SNPs in
Interferon gamma: https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-6-82
Human-leukocyte antigen classes https://www.ncbi.nlm.nih.gov/pubmed/21958371
Il-18 https://www.ncbi.nlm.nih.gov/pubmed/16652313
IL-1A PMID : 21958371
RelB (reticuloendotheliosis viral oncogene homolog B) PMID : 21958371
FGL2 (fibrinogen-like protein 2) PMID : 21958371
That is all the research I could find on SARS and genetic mutations, but not an exhaustive search.
It is too early to say if these same associations will hold true for Covid 19. It only shares 80% of genetic similarity with SARS. That 20% of difference could turn out too be hugely important it how it interacts with our immune system. Already doctors in China have made the observation that COvid provokes a different cytokine storm than SARS. Meaning, the cascade of inflammatory chemokine, interleukins, etc is made up of different molecules. For example: “Interleukin 17 blockade might benefit those patients who have a 2019-nCoV infection and increased plasma concentration of interleukin 17. Source: https://www.ncbi.nlm.nih.gov/pubmed/32035018
Asians do have a increased incidence (30ish %) well known functional SNP in the IL-gene that dramatically unregulated IL-17 as compared to Caucasians (12ish%) so this would be an obvious angle to investigate, IMO.
There has been just published a non peer reviewed paper (Profiling the Immune Vulnerability Landscape of the 2019 Novel Coronavirus) and authors concluded Asians may be at increased risk due to T and B cell epitope differences. https://www.preprints.org/manuscript/202002.0167/v1
Only time and more research will tell if there are some genetic mutations that make more people/ethnicities that help or harm in regards to Covid 19.
Claire