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

Autor: El-Sayed Moustafa JS; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Jackson AU; Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Brotman SM; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA., Guan L; Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA., Villicaña S; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Roberts AL; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Zito A; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Genetics, Harvard Medical School, Boston, MA 02115; USA., Bonnycastle L; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Erdos MR; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Narisu N; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Stringham HM; Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Welch R; Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Yan T; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Lakka T; Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio, Finland.; Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, University of Eastern Finland, Kuopio, Finland., Parker S; Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA., Tuomilehto J; Public Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.; Department of Public Health, University of Helsinki, Helsinki, Finland.; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia., Collins FS; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Pajukanta P; Department of Human Genetics and Institute for Precision Health, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Boehnke M; Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Koistinen HA; Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland.; University of Helsinki and Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.; Minerva Foundation Institute for Medical Research, Helsinki, Finland., Laakso M; Department of Medicine, University of Eastern Finland, Kuopio, Finland.; Kuopio University Hospital, Kuopio, Finland., Falchi M; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Bell JT; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK., Scott LJ; Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI, USA., Mohlke KL; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA., Small KS; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2020 Aug 14. Date of Electronic Publication: 2020 Aug 14.
DOI: 10.1101/2020.08.11.20171108
Abstrakt: 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.
Databáze: MEDLINE