Abstract
Smoking could predispose individuals to a more severe COVID-19 by upregulating a particular gene known as mdig, which is mediated through a number of well-known histone modifications. Smoking might regulate the transcription-activating H3K4me3 mark, along with the transcription-repressing H3K9me3 and H3K27me3 marks, in a way to favor SARS-CoV-2 entry by enhancing the expression of ACE2, NRP1 and NRP2, AT1R, CTSD and CTSL, PGE2 receptors 2-4, SLC6A20 and IL-6, all of which interact either directly or indirectly with important receptors, facilitating viral entry in COVID-19.
Keywords:
COVID-19; H3K27me3; H3K4me3; HeK9me3; SARS-CoV-2; epigenetic gene regulation; epigenetics and disease; histone modifications; mdig; smoking.
Plain language summary
Lay abstract The role of smoking in development of several respiratory diseases has been clearly established. A significant proportion of these deleterious effects is mediated through epigenetic mechanisms, particularly histone modifications. Recent evidence indicates that smoking induces the expression of a mediator known as mdig, which in turn alters the transcription of several key proteins that have been implicated in development of COVID-19.
MeSH terms
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Angiotensin-Converting Enzyme 2 / genetics
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Angiotensin-Converting Enzyme 2 / metabolism
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COVID-19 / diagnosis
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COVID-19 / genetics*
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COVID-19 / metabolism
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COVID-19 / virology
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Cathepsin D / genetics
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Cathepsin D / metabolism
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Cathepsin L / genetics
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Cathepsin L / metabolism
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Dioxygenases / genetics*
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Dioxygenases / metabolism
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Epigenesis, Genetic*
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Histone Demethylases / genetics*
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Histone Demethylases / metabolism
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Histones / genetics*
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Histones / metabolism
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Humans
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Methylation
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Neuropilin-1 / genetics
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Neuropilin-1 / metabolism
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Neuropilin-2 / genetics
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Neuropilin-2 / metabolism
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Processing, Post-Translational*
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Receptor, Angiotensin, Type 1 / genetics
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Receptor, Angiotensin, Type 1 / metabolism
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Receptors, Prostaglandin E / genetics
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Receptors, Prostaglandin E / metabolism
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Risk Factors
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SARS-CoV-2 / genetics
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SARS-CoV-2 / growth & development
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SARS-CoV-2 / metabolism
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Smoking / genetics*
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Smoking / metabolism
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Smoking / pathology
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Virus Internalization
Substances
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AGTR1 protein, human
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Histones
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IL6 protein, human
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Interleukin-6
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Membrane Transport Proteins
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NRP1 protein, human
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Neuropilin-2
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Nuclear Proteins
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Protein Isoforms
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Receptor, Angiotensin, Type 1
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Receptors, Prostaglandin E
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SLC6A20 protein, human
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histone H3 trimethyl Lys4
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neuropilin-2, human
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Neuropilin-1
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Dioxygenases
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Histone Demethylases
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RIOX2 protein, human
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ACE2 protein, human
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Angiotensin-Converting Enzyme 2
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CTSL protein, human
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Cathepsin L
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CTSD protein, human
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Cathepsin D