ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19.
ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19.
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DOI：
10.1038/s41366-022-01136-w
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发表时间：
2022-08
影响因子：
4.9
通讯作者：
Small, Kerrin S.
中科院分区：
文献类型：
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作者：
Moustafa, Julia S. El-Sayed;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.
COVID-19 的严重程度差异很大。尽管一些人口和心脏代谢因素（包括年龄和肥胖）与严重疾病风险增加相关，但其潜在机制尚不确定。在对总共 1471 名参与者的三项独立研究的荟萃分析中，我们研究了与皮下脂肪组织血管紧张素 I 转换酶 2 (ACE2) 表达相关的表型和遗传因素，通过 RNA-Seq 进行测量，ACE2 充当 SARS-CoV-2 细胞进入的受体。较低的脂肪组织ACE2表达与多种不利的心脏代谢健康指标相关，包括2型糖尿病（T2D）（P = 9.14×10−6）、肥胖状态（P = 4.81 × 10−5）、较高的血清空腹胰岛素（P = 5.32 × 10−4）、BMI (P = 3.94 × 10−4)，并降低血清HDL水平(P = 1.92 × 10−7)。 ACE2表达还与脂肪组织中细胞类型的估计比例相关：较低的表达与微血管内皮细胞比例较低（P = 4.25 × 10−4）和巨噬细胞比例较高（P = 2.74 × 10−5）相关。尽管估计遗传力为 32%，但我们没有发现任何与脂肪组织 ACE2 表达相关的近端或远端表达数量性状位点 (eQTL)。我们的结果表明，具有已知会增加严重 COVID-19 风险的心脏代谢特征的个体在这种高度相关的组织中具有较低的背景 ACE2 水平。脂肪组织 ACE2 表达减少可能有助于心脏代谢疾病的病理生理学，以及相关的重症 COVID-19 风险增加。
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. 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. Lower adipose tissue ACE2 expression was associated with multiple adverse cardio-metabolic health indices, including type 2 diabetes (T2D) (P = 9.14 × 10−6), obesity status (P = 4.81 × 10−5), higher serum fasting insulin (P = 5.32 × 10−4), BMI (P = 3.94 × 10−4), and lower serum HDL levels (P = 1.92 × 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 × 10−4) and higher proportion of macrophages (P = 2.74 × 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. 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.
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影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
64.8
作者：
Imai Y;Kuba K;Rao S;Huan Y;Guo F;Guan B;Yang P;Sarao R;Wada T;Leong-Poi H;Crackower MA;Fukamizu A;Hui CC;Hein L;Uhlig S;Slutsky AS;Jiang C;Penninger JM
通讯作者：
Penninger JM
影响因子：
64.8
作者：
Crackower, MA;Sarao, R;Penninger, JM
通讯作者：
Penninger, JM