While the majority of confirmed COVID-19 cases result in mild symptoms, the virus does pose a serious threat to certain people.
Morbidity and mortality rates rise dramatically with age and co-existing health conditions, such as cancer and heart disease.
However, even young and otherwise healthy people have unpredictably experienced severe illness and death.
These clinical observations suggest that genetic factors may influence COVID-19 disease susceptibility, but these factors remain largely unknown.
In a recent study at Cleveland Clinic, researchers identified genetic factors that may influence the risk of COVID-19.
The findings could guide personalized treatment for COVID-19.
The study is published in BMC Medicine. One author is Feixiong Cheng, Ph.D., Genomic Medicine Institute.
In the study, the team examined genetic susceptibility to COVID-19 by examining DNA polymorphisms (variations in DNA sequences) in the ACE2 and TMPRSS2 genes.
ACE2 and TMPRSS2 produce enzymes (ACE2 and TMPRSS2, respectively) that enable the virus to enter and infect human cells.
Looking at 81,000 human genomes from three genomic databases, they found 437 non-synonymous single-nucleotide variants in the protein-coding regions of ACE2 and TMPRSS2.
They identified multiple potentially deleterious polymorphisms in both genes (63 in ACE2; 68 in TMPRSS2) that offer potential explanations for different genetic susceptibility to COVID-19 as well as for risk factors.
Several ACE2 variants were found to be associated with cardiovascular and pulmonary conditions by potentially altering the angiotensinogen-ACE2.
In addition, germline deleterious variants in the coding region of TMPRSS2, a key gene in prostate cancer, were found to occur in different cancer types, suggesting that oncogenic roles of TMPRSS2 may be linked to poor outcomes with COVID-19.
These findings show a possible link between ACE2 and TMPRSS2 polymorphisms and COVID-19 susceptibility, and indicate that a systematic investigation of the functional polymorphisms these variants among different populations could pave the way for precision medicine and personalized treatment strategies for COVID-19.
However, all tests in this study were performed in general populations, not with COVID-19 patient genetic data.
Therefore, the team calls for a human genome initiative to validate his findings and to identify new clinically actionable variants to accelerate precision medicine for COVID-19.
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