期刊
INTERNATIONAL JOURNAL OF OBESITY
卷 46, 期 8, 页码 1478-1486出版社
SPRINGERNATURE
DOI: 10.1038/s41366-022-01136-w
关键词
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资金
- Medical Research Council [MR/M004422/1, MR/R023131/1]
- Wellcome Trust
- Versus Arthritis
- European Union Horizon 2020
- Chronic Disease Research Foundation (CDRF)
- Zoe Ltd
- National Institute for Health and Care Research (NIHCR) Clinical Research Network (CRN)
- Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust
- King's College London
- US National Institutes of Health (NIH) [U01DK062370, 1-ZIA-HG000024, R01DK093757, R01DK072193, P01HL28481]
- Academy of Finland [271961, 272741, 258753]
- National Institute of General Medical Sciences [5T32 GM007092]
- Global Partnership Award
- UNC Global for travel fund
- National Council of Science and Technology of Mexico (CONACYT)
- King's Together Rapid COVID-19 Call award
- Wellcome [221574/Z/20/Z]
- Maudsley Charity
- Guy's & St. Thomas' Charity [TR130505]
- Wellcome Trust [221574/Z/20/Z] Funding Source: Wellcome Trust
- Academy of Finland (AKA) [272741, 272741, 271961, 271961] Funding Source: Academy of Finland (AKA)
This study investigates the underlying mechanisms of COVID-19 severity in relation to obesity and other cardio-metabolic factors. The results show that individuals with lower background ACE2 levels, which is associated with adverse cardio-metabolic health indices, are at increased risk of severe COVID-19.
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.
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