The rs738409 G Allele in PNPLA3 Is Associated With a Reduced Risk of COVID-19 Mortality and Hospitalization

Authors: Innes, Hamish ;

Buch, Stephan;

Barnes, Eleanor ;

Hampe, Jochen;

Marjot, Thomas ;

Stickel, Felix

Source: Gastroenterology

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: https://doi.org/10.1053/j.gastro.2021.02.059

Abstract

The natural history of SARS-CoV-2 infection is highly variable, ranging from asymptomatic infection on one hand to pneumonia, septic shock, multiple organ failure, and death on the other. The physiologic pathways that influence prognosis after infection are still incompletely understood; this represents a key barrier to optimal management.

The rs738409 G variant in PNPLA3 (patatin-like phospholipase domain containing 3) is a prominent genetic risk factor for steatosis, cirrhosis, and hepatocellular carcinoma. For 2 reasons, we hypothesized that rs738409 G may also affect COVID-19 severity. First, rs738409 G is associated with retinoid storage levels in liver mesenchymal cells, which may have a bearing on the ability to mount an effective immune response after viral infection. Second, previous data suggest that rs738409 G increases the cellular abundance of omega-3 polyunsaturated fatty acids, such as alpha linolenic acid, which may modulate inflammatory process levels during infections.

Our goal was to test a possible association of rs738409 G in PNPLA3 with outcomes of COVID-19 using data from the United Kingdom Biobank (UKB) study.

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Innes, H., Buch, S., Barnes, E., Hampe, J., Marjot, T. & Stickel, F. 2021, 'The rs738409 G Allele in PNPLA3 Is Associated With a Reduced Risk of COVID-19 Mortality and Hospitalization', Gastroenterology. https://doi.org/10.1053/j.gastro.2021.02.059

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DOI: https://doi.org/10.1053/j.gastro.2021.02.059