Do genetic polymorphisms in angiotensin converting enzyme 2 (ACE2) gene play a role in coronavirus disease 2019 (COVID-19)?

• Published in: Clinical chemistry and laboratory medicine Vol. 58; no. 9; pp. 1415 - 1422
• Main Authors: Lippi, Giuseppe, Lavie, Carl J., Henry, Brandon M., Sanchis-Gomar, Fabian
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 27.08.2020; Walter De Gruyter & Company
• Subjects: ACE2; ACE2 gene; Adipose tissue; Angiotensin; Angiotensin-Converting Enzyme 2; Betacoronavirus - physiology; Coronaviridae; Coronavirus Infections - physiopathology; Coronaviruses; COVID-19; Environmental factors; enzyme; Enzymes; Fibrosis; Gastrointestinal system; Gene polymorphism; Genetic screening; Health risks; Humans; Lymphocytes; Oxidation; Pandemics; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - physiopathology; polymorphism; Polymorphism, Genetic; Protein Binding; Protein Domains; Proteins; receptor; Receptors, Virus - chemistry; Receptors, Virus - genetics; Receptors, Virus - metabolism; Respiratory diseases; Respiratory tract; Risk; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Vasoconstriction; Viral diseases; Viruses; COVID-19; enzyme; angiotensin; polymorphism; receptor
• ISSN: 1434-6621; 1437-4331; 1437-4331
• DOI: 10.1515/cclm-2020-0727

Although some demographic, clinical and environmental factors have been associated with a higher risk of developing coronavirus disease 2019 (COVID-19) and progressing towards severe disease, altogether these variables do not completely account for the different clinical presentations observed in patients with comparable baseline risk, whereby some subjects may remain totally asymptomatic, whilst others develop a very aggressive illness. Some predisposing genetic backgrounds can hence potentially explain the broad inter-individual variation of disease susceptibility and/or severity. It has been now clearly established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, infects the host cell through biding and being internalized with angiotensin converting enzyme 2 (ACE2), a surface protein expressed in a noticeable number of human cells, especially in those of upper and lower respiratory tracts, heart, kidney, testis, adipose tissue, gastrointestinal system and in lymphocytes. Accumulating evidence now suggests that genetic polymorphisms in the gene may modulate intermolecular interactions with the spike protein of SARS-CoV-2 and/or contribute to pulmonary and systemic injury by fostering vasoconstriction, inflammation, oxidation and fibrosis. We hence argue that the development of genetic tests aimed at specifically identifying specific COVID-19-susceptible or -protective variants in the general population may be a reasonable strategy for stratifying the risk of infection and/or unfavorable disease progression.