ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition
Julia Sarah El-Sayed Moustafa,
Anne U. Jackson,
Sarah M. Brotman,
Amy L Roberts,
Michael R Erdos,
Heather M Stringham,
Ryan P. Welch,
Francis S Collins,
Heikki A Koistinen,
Jordana T. Bell,
Laura J Scott,
Karen L. Mohlke,
Kerrin S Small
Posted 14 Aug 2020
medRxiv DOI: 10.1101/2020.08.11.20171108
Posted 14 Aug 2020
COVID-19 severity has varied widely, with demographic and cardio-metabolic factors increasing risk of severe reactions to SARS-CoV-2 infection, but the underlying mechanisms for this remain uncertain. We investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 (ACE2), which has been shown to act as a receptor for SARS-CoV-2 cellular entry. In a meta-analysis of three independent studies including up to 1,471 participants, lower adipose tissue ACE2 expression was associated with adverse cardio-metabolic health indices including type 2 diabetes (T2D) and obesity status, higher serum fasting insulin and BMI, and lower serum HDL levels (P<5.32x10-4). ACE2 expression levels were also associated with estimated proportions of cell types in adipose tissue; lower ACE2 expression was associated with a lower proportion of microvascular endothelial cells (P=4.25x10-4) and higher macrophage proportion (P=2.74x10-5), suggesting a link to inflammation. Despite an estimated heritability of 32%, we did not identify any proximal or distal genetic variants (eQTLs) associated with adipose tissue ACE2 expression. Our results demonstrate that at-risk individuals have lower background ACE2 levels in this highly relevant tissue. Further studies will be required to establish how this may contribute to increased COVID-19 severity.
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