Lack of Evidence for a Role of ACE-2 Polymorphisms as a Bedside Clinical Prognostic Marker of COVID-19
Josè R. Fiore,
Mariantonietta Di Stefano,
Andrew Oler,
Yu Zhang,
Jingwen Gu,
Clifton L. Dalgard,
Giuseppina Faleo,
Brian Epling,
Luigi Notarangelo,
Andrea Lisco,
Teresa A. Santantonio
Affiliations
Josè R. Fiore
Infectious Diseases Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
Mariantonietta Di Stefano
Infectious Diseases Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
Andrew Oler
Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA
Yu Zhang
Immune Deficiency Genetics Disease Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease (NIAID), Division of Intramural Research (DIR), National Institutes of Health, Bethesda, MD 20892, USA
Jingwen Gu
Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA
Clifton L. Dalgard
Collaborative Health Initiative Research Program, The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD 20892, USA
Giuseppina Faleo
Infectious Diseases Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
Brian Epling
National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA
Luigi Notarangelo
Immune Deficiency Genetics Disease Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease (NIAID), Division of Intramural Research (DIR), National Institutes of Health, Bethesda, MD 20892, USA
Andrea Lisco
National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA
Teresa A. Santantonio
Infectious Diseases Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
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.
