Lack of Evidence for a Role of ACE-2 Polymorphisms as a Bedside Clinical Prognostic Marker of COVID-19

• Published in: Viruses 2023-06, Vol.15 (7), p.1448
• Main Authors: Fiore, Josè R, Di Stefano, Mariantonietta, Oler, Andrew, Zhang, Yu, Gu, Jingwen, Dalgard, Clifton L, Faleo, Giuseppina, Epling, Brian, Notarangelo, Luigi, Lisco, Andrea, Santantonio, Teresa A
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin; Angiotensin converting enzyme; Angiotensin-converting enzyme 2; angiotensin-converting enzyme 2 (ACE-2); Asymptomatic; Biological markers; Brief Report; Coronaviruses; COVID-19; Deoxyribonucleic acid; Disease transmission; DNA; Gastrointestinal tract; Gene polymorphism; Genetic aspects; Genetic polymorphisms; Genetic testing; Genomes; Glycoproteins; Health aspects; HIV; Hospitals; Human immunodeficiency virus; Infections; Infectious diseases; Medical research; Medicine, Experimental; Nucleotide sequence; Pathogenesis; Patients; Peptidyl-dipeptidase A; Pneumonia; Post-transcription; Proteins; Respiratory diseases; respiratory distress syndrome (ARDS); Respiratory failure; Severe acute respiratory syndrome coronavirus 2; severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); single nucleotide polymorphism (SNP); Whole genome sequencing
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15071448

The novel SARS-CoV-2 coronavirus causes a severe respiratory syndrome referred to as coronavirus disease (COVID-19). The angiotensin-converting enzyme 2 (ACE-2) plays an important role as a cellular receptor for SARS-CoV-2 and is largely expressed in lungs, kidneys, heart and the gastrointestinal tract along with being shed in plasma. The ACE-2 gene and protein show a high level of genetic polymorphism, including simple nucleotide variation, transcriptional variation, post-transcriptional changes, and putative protein mutations that could interfere with the binding or entry of SARS-CoV-2 and affect tissue damage in lungs or other organs. Genetic polymorphisms can impact SARS-CoV-2 viral entry and COVID-19 severity. This single-center study evaluated the possible role of the main ACE-2 polymorphisms (rs143936283, rs2285666, rs41303171, rs35803318, and rs2106809) as potential prognostic markers in SARS-CoV-2-infected individuals. Frozen whole blood was used for DNA isolation and genomic DNA samples were sheared using the Covaris LE220 Focused-ultrasonicator for targeting a peak size of 410 bp. Whole-genome sequencing libraries were generated from fragmented DNA using the Illumina TruSeq DNA PCR-Free HT Library Preparation Kit and sequenced on an Illumina NovaSeq 6000. We did not identify any correlation between ACE-2 polymorphisms and COVID-19 prognosis, suggesting that the interpretation and clinical use of ACE-2 genetic polymorphisms in real-world clinical settings requires further experimental and clinical validation.