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<jats:title>Abstract</jats:title><jats:p>The SARS-CoV-2 pandemic has resulted in widespread morbidity and mortality globally. <jats:italic>ACE2</jats:italic> is a receptor for SARS-CoV-2 and differences in expression may affect susceptibility to COVID-19. Using HCV-infected liver tissue from 195 individuals, we discovered that among genes negatively correlated with <jats:italic>ACE2</jats:italic>, interferon signalling pathways were highly enriched and observed down-regulation of <jats:italic>ACE2</jats:italic> after interferon-alpha treatment. Negative correlation was also found in the gastrointestinal tract and in lung tissue from a murine model of SARS-CoV-1 infection suggesting conserved regulation of <jats:italic>ACE2</jats:italic> across tissue and species. Performing a genome-wide eQTL analysis, we discovered that polymorphisms in the interferon lambda (<jats:italic>IFNL</jats:italic>) region are associated with <jats:italic>ACE2</jats:italic> expression. Increased <jats:italic>ACE2</jats:italic> expression in the liver was also associated with age and presence of cirrhosis. Polymorphisms in the <jats:italic>IFNL</jats:italic> region may impact not only antiviral responses but also <jats:italic>ACE2</jats:italic> with potential consequences for clinical outcomes in distinct ethnic groups and with implications for therapeutic interventions.</jats:p>

Original publication




Journal article


Cold Spring Harbor Laboratory

Publication Date