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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1448
Issue number7
StatePublished - Jul 2023
Externally publishedYes


  • angiotensin-converting enzyme 2 (ACE-2)
  • respiratory distress syndrome (ARDS)
  • severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
  • single nucleotide polymorphism (SNP)


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