Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: A rather controversial hypothesis. A case-control study.

Content Provider	Europe PMC
Author	Papadopoulou, Anna Fragkou, Paraskevi C. Maratou, Eirini Dimopoulou, Dimitra Kominakis, Antonis Kokkinopoulou, Ioanna Kroupis, Christos Nikolaidou, Athina Antonakos, Georgios Papaevangelou, Vasiliki Armaganidis, Apostolos Tsantes, Argirios Polyzogopoulou, Eftychia Tsiodras, Sotirios Antoniadou, Anastasia Moutsatsou, Paraskevi
Abstract	Accumulating data has shown a contribution of the renin‐angiotensin system in COVID‐19 pathogenesis. The role of angiotensin‐converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID‐19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case‐control study and assessed the impact of ACE I/D genotype in COVID‐19 disease prevalence and severity. In 81 COVID‐19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID‐19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0‐fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266–2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051–1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 ± 0.26) than in controls (4.65 ± 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 ± 0.29 vs. 5.38 ± 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID‐19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID‐19 patients compared to healthy individuals and set the grounds for large‐scale studies assessing ACE genotype‐based optimized therapies with ACE inhibitors and angiotensin receptor blockers.
Page Count	10
ISSN	01466615
Journal	Journal of Medical Virology
Volume Number	94
PubMed Central reference number	PMC8661574
Issue Number	3
PubMed reference number	34708878
e-ISSN	10969071
DOI	10.1002/jmv.27417
Language	English
Publisher	John Wiley and Sons Inc.
Publisher Date	2021-11-05
Publisher Place	Hoboken
Access Restriction	Open
Rights License	This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency. © 2021 Wiley Periodicals LLC
Subject Keyword	ACE angiotensin converting enzyme COVID‐19 ACE polymorphism ACE activity SARS‐CoV‐2
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Virology