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

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dc.contributor.author El-Sayed Moustafa , J. S.
dc.contributor.author Jackson, Anne U.
dc.contributor.author Brotman, Sarah M.
dc.contributor.author Guan, Li
dc.contributor.author Villicana, Sergio
dc.contributor.author Roberts, Amy L.
dc.contributor.author Zito, Antonino
dc.contributor.author Bonnycastle, Lori
dc.contributor.author Erdos, Michael R.
dc.contributor.author Narisu, Narisu
dc.contributor.author Stringham, Heather M.
dc.contributor.author Welch, Ryan
dc.contributor.author Yan, Tingfen
dc.contributor.author Lakka, Timo
dc.contributor.author Parker, Stephen
dc.contributor.author Tuomilehto, Jaakko
dc.contributor.author Seow, Jeffrey
dc.contributor.author Graham, Carl
dc.contributor.author Huettner, Isabella
dc.contributor.author Acors, Sam
dc.contributor.author Kouphou, Neophytos
dc.contributor.author Wadge, Samuel
dc.contributor.author Duncan, Emma L.
dc.contributor.author Steves, Claire J.
dc.contributor.author Doores, Katie J.
dc.contributor.author Malim, Michael H.
dc.contributor.author Collins, Francis S.
dc.contributor.author Pajukanta, Paivi
dc.contributor.author Boehnke, Michael
dc.contributor.author Koistinen, Heikki A.
dc.contributor.author Laakso, Markku
dc.contributor.author Falchi, Mario
dc.contributor.author Bell, Jordana T.
dc.contributor.author Scott, Laura J.
dc.contributor.author Mohlke, Karen L.
dc.contributor.author Small, Kerrin S.
dc.date.accessioned 2022-08-04T05:56:04Z
dc.date.available 2022-08-04T05:56:04Z
dc.date.issued 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 . https://doi.org/10.1038/s41366-022-01136-w
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.identifier.uri http://hdl.handle.net/10138/346665
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 ANGIOTENSIN-CONVERTING ENZYME-2
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.doi https://doi.org/10.1038/s41366-022-01136-w
dc.relation.issn 0307-0565
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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