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ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition
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 expressi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430606/ https://www.ncbi.nlm.nih.gov/pubmed/32817962 http://dx.doi.org/10.1101/2020.08.11.20171108 |
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author | El-Sayed Moustafa, Julia S. Jackson, Anne U. Brotman, Sarah M. Guan, Li Villicaña, Sergio Roberts, Amy L. Zito, Antonino Bonnycastle, Lori Erdos, Michael R. Narisu, Narisu Stringham, Heather M. Welch, Ryan Yan, Tingfen Lakka, Timo Parker, Stephen Tuomilehto, Jaakko Collins, Francis S. Pajukanta, Päivi Boehnke, Michael Koistinen, Heikki A. Laakso, Markku Falchi, Mario Bell, Jordana T. Scott, Laura J. Mohlke, Karen L. Small, Kerrin S. |
author_facet | El-Sayed Moustafa, Julia S. Jackson, Anne U. Brotman, Sarah M. Guan, Li Villicaña, Sergio Roberts, Amy L. Zito, Antonino Bonnycastle, Lori Erdos, Michael R. Narisu, Narisu Stringham, Heather M. Welch, Ryan Yan, Tingfen Lakka, Timo Parker, Stephen Tuomilehto, Jaakko Collins, Francis S. Pajukanta, Päivi Boehnke, Michael Koistinen, Heikki A. Laakso, Markku Falchi, Mario Bell, Jordana T. Scott, Laura J. Mohlke, Karen L. Small, Kerrin S. |
author_sort | El-Sayed Moustafa, Julia S. |
collection | PubMed |
description | 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<5.32×10(−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=4.25×10(−4)) and higher macrophage proportion (P=2.74×10(−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. |
format | Online Article Text |
id | pubmed-7430606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-74306062020-08-18 ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition El-Sayed Moustafa, Julia S. Jackson, Anne U. Brotman, Sarah M. Guan, Li Villicaña, Sergio Roberts, Amy L. Zito, Antonino Bonnycastle, Lori Erdos, Michael R. Narisu, Narisu Stringham, Heather M. Welch, Ryan Yan, Tingfen Lakka, Timo Parker, Stephen Tuomilehto, Jaakko Collins, Francis S. Pajukanta, Päivi Boehnke, Michael Koistinen, Heikki A. Laakso, Markku Falchi, Mario Bell, Jordana T. Scott, Laura J. Mohlke, Karen L. Small, Kerrin S. medRxiv Article 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<5.32×10(−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=4.25×10(−4)) and higher macrophage proportion (P=2.74×10(−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. Cold Spring Harbor Laboratory 2020-08-14 /pmc/articles/PMC7430606/ /pubmed/32817962 http://dx.doi.org/10.1101/2020.08.11.20171108 Text en http://creativecommons.org/licenses/by/4.0/It is made available under a CC-BY 4.0 International license (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article El-Sayed Moustafa, Julia S. Jackson, Anne U. Brotman, Sarah M. Guan, Li Villicaña, Sergio Roberts, Amy L. Zito, Antonino Bonnycastle, Lori Erdos, Michael R. Narisu, Narisu Stringham, Heather M. Welch, Ryan Yan, Tingfen Lakka, Timo Parker, Stephen Tuomilehto, Jaakko Collins, Francis S. Pajukanta, Päivi Boehnke, Michael Koistinen, Heikki A. Laakso, Markku Falchi, Mario Bell, Jordana T. Scott, Laura J. Mohlke, Karen L. Small, Kerrin S. ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition |
title | ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition |
title_full | ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition |
title_fullStr | ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition |
title_full_unstemmed | ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition |
title_short | ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition |
title_sort | ace2 expression in adipose tissue is associated with covid-19 cardio-metabolic risk factors and cell type composition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430606/ https://www.ncbi.nlm.nih.gov/pubmed/32817962 http://dx.doi.org/10.1101/2020.08.11.20171108 |
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