Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: A rather controversial hypothesis. A case-control study.
J Med Virol
; 94(3): 1050-1059, 2022 03.
Article
in English
| MEDLINE | ID: covidwho-1487497
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peptidyl-Dipeptidase A
/
COVID-19
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
J Med Virol
Year:
2022
Document Type:
Article
Affiliation country:
Jmv.27417
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