An Epigenetic Signature for Susceptibility to Severe COVID-19

by Michael A. Goldman,* PhD, Professor & Former Chair, Biology, San Francisco State University (SFSU).

Although COVID-19 is an infectious disease, caused by exposure to the now not-so-novel coronavirus, SARS-CoV-2, the degree to which an individual person is affected by COVID-19, if at all, is in part due to host genetic factors. One of the hallmarks of COVID-19 is the way in which some individuals experience no, or very mild, symptoms, while others end up on respirators, dying, or having long-term effects (called long-COVID). Potential host genetic factors have been identified by genome-wide association studies (GWAS), in regions 3p21.31, 12q24.13, the ABO blood group system, and a type I interferon immunity defect. While the current pandemic is yielding to public health measures and highly successful vaccines, produced in record time, a fundamental understanding of the host factors that influence disease risk can be of tremendous value in preparing for future epidemics and in rapidly putting an end to COVID-19. New studies show that, in addition to host genetics, which involves heritable variation at the DNA sequence level, changes at the epigenetic level, such as DNA methylation, may also be involved. The most common form of DNA methylation in mammals involves the conversion and subsequent propagation of a cytosine in a CpG dinucleotide into a 5-methyl-cytosine. Occurring in critical regulatory regions of the genome, CpG methylation often silences gene expression. In vitro drug treatment of rodent-human hybrid cells with 5-aza-cytidine can reverse methylation and re-activate previously silent genes, such as those on the inactive X chromosome in human females.

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