Scientists led by the Storr Liver Centre at the University of Sydney’s Westmead Institute for Medical Research have identified a gene — called membrane bound o-acyltransferase domain containing 7 (MBOAT7) — associated with the severity of both COVID-19 and metabolic dysfunction associated fatty liver disease (MAFLD).
Creative rendition of SARS-CoV-2, displaying 3D prints of virus particles (colorized red and teal/blue; the red virus surface is covered with teal/blue spike proteins that enable the virus to enter and infect human cells), and a background image that is a colorized scanning electron micrograph of a cell (blue) infected with the Omicron strain of the virus (red). Image credit: NIAID.
MAFLD affects one-in-four adults and nearly one-in-10 children worldwide. Globally, it is the most frequent kind of chronic liver disease.
“Liver disease is a silent killer. Most people don’t know they have a liver problem until it’s advanced and they develop liver scarring, liver cirrhosis and, in severe cases, liver failure and deadly cancer,” said University of Sydney’s Dr. Jawaher Alharthi and her colleagues.
“Its complications, however, are not limited to liver disease.”
“It is strongly associated with several other cardiometabolic diseases such as Type 2 diabetes and cardiovascular diseases.”
“In response to COVID-19, the host (humans) mounts an immune response whose delicate balance determines the course of illness.”
“Severe COVID-19 is associated with exacerbated immune and hyperinflammatory responses and inflammatory macrophages can induce a cytokine storm leading to tissue damage. “
In the new study, Dr. Alharthi and co-authors discovered how COVID-19 increases the risk of MAFLD and how is the latter increasing the severity of COVID-19, aiding the development of potential treatments for these patients.
“The relationship between fatty liver disease and COVID-19 considered a bit of a mystery, as we do not know how and why both diseases increases the risk of each other,” Dr. Alharthi said.
“We conducted a large and detailed genetic and molecular study and identified a gene, MBOAT7, associated with the severity of both MAFLD and COVID-19.”
“This gene, plays an important role in the regulation of immune and inflammatory responses upon COVID-19.”
“A disruption in the activity of the MBOAT7 gene could increase the chances of increase cytokines production and tissues damage and liver disease.”
“Interestingly, we also identified that disruption of MBOAT7 may ‘preprogram’ the cell epigenome (a set of markers that determines not just gene expression, but genes themselves and influenced by environment, diet, and hormones) and prime it to respond severely to even a weak stimulation upon COVID-19 that ultimately increases tissue damage.”
A paper on the findings was published in the journal Nature Communications.
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J. Alharthi et al. 2022. A metabolic associated fatty liver disease risk variant in MBOAT7 regulates toll like receptor induced outcomes. Nat Commun 13, 7430; doi: 10.1038/s41467-022-35158-9
