ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19

Show simple item record El-Sayed Moustafa , J. S. Jackson, Anne U. Brotman, Sarah M. Guan, Li Villicana, 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 Seow, Jeffrey Graham, Carl Huettner, Isabella Acors, Sam Kouphou, Neophytos Wadge, Samuel Duncan, Emma L. Steves, Claire J. Doores, Katie J. Malim, Michael H. Collins, Francis S. Pajukanta, Paivi Boehnke, Michael Koistinen, Heikki A. Laakso, Markku Falchi, Mario Bell, Jordana T. Scott, Laura J. Mohlke, Karen L. Small, Kerrin S. 2022-08-04T05:56:04Z 2022-08-04T05:56:04Z 2022-08
dc.identifier.citation El-Sayed Moustafa , J S , Jackson , A U , Brotman , S M , Guan , L , Villicana , S , Roberts , A L , Zito , A , Bonnycastle , L , Erdos , M R , Narisu , N , Stringham , H M , Welch , R , Yan , T , Lakka , T , Parker , S , Tuomilehto , J , Seow , J , Graham , C , Huettner , I , Acors , S , Kouphou , N , Wadge , S , Duncan , E L , Steves , C J , Doores , K J , Malim , M H , Collins , F S , Pajukanta , P , Boehnke , M , Koistinen , H A , Laakso , M , Falchi , M , Bell , J T , Scott , L J , Mohlke , K L & Small , K S 2022 , ' ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19 ' , International Journal of Obesity , vol. 46 , no. 8 , pp. 1478-1486 .
dc.identifier.other PURE: 212609773
dc.identifier.other PURE UUID: 4ddc799f-e126-4506-948e-e5c0842fafb6
dc.identifier.other WOS: 000799460800002
dc.identifier.other ORCID: /0000-0001-7870-070X/work/116874526
dc.description.abstract Background COVID-19 severity varies widely. Although some demographic and cardio-metabolic factors, including age and obesity, are associated with increasing risk of severe illness, the underlying mechanism(s) are uncertain. Subjects/methods In a meta-analysis of three independent studies of 1471 participants in total, we investigated phenotypic and genetic factors associated with subcutaneous adipose tissue expression of Angiotensin I Converting Enzyme 2 (ACE2), measured by RNA-Seq, which acts as a receptor for SARS-CoV-2 cellular entry. Results Lower adipose tissue ACE2 expression was associated with multiple adverse cardio-metabolic health indices, including type 2 diabetes (T2D) (P = 9.14 x 10(-6)), obesity status (P = 4.81 x 10(-5)), higher serum fasting insulin (P = 5.32 x 10(-4)), BMI (P = 3.94 x 10(-4)), and lower serum HDL levels (P = 1.92 x 10(-7)). ACE2 expression was also associated with estimated proportions of cell types in adipose tissue: lower expression was associated with a lower proportion of microvascular endothelial cells (P = 4.25 x 10(-4)) and higher proportion of macrophages (P = 2.74 x 10(-5)). Despite an estimated heritability of 32%, we did not identify any proximal or distal expression quantitative trait loci (eQTLs) associated with adipose tissue ACE2 expression. Conclusions Our results demonstrate that individuals with cardio-metabolic features known to increase risk of severe COVID-19 have lower background ACE2 levels in this highly relevant tissue. Reduced adipose tissue ACE2 expression may contribute to the pathophysiology of cardio-metabolic diseases, as well as the associated increased risk of severe COVID-19. en
dc.format.extent 9
dc.language.iso eng
dc.relation.ispartof International Journal of Obesity
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19 en
dc.type Article
dc.contributor.organization Clinicum
dc.contributor.organization Department of Public Health
dc.contributor.organization University of Helsinki
dc.contributor.organization Department of Medicine
dc.contributor.organization HUS Internal Medicine and Rehabilitation
dc.description.reviewstatus Peer reviewed
dc.relation.issn 0307-0565
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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