ACE2 Polymorphisms and COVID-19 Severity: A Study on Their Relationship with Clinical Findings

Area of Science:

• Genetics and Genomics
• Infectious Diseases
• Molecular Biology

Background:

• Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) causes COVID-19, with disease severity linked to angiotensin-converting enzyme 2 (ACE2) gene expression.
• ACE2 receptor interaction with the SARS-CoV-2 spike protein is crucial for viral entry.
• Genetic variations in the ACE2 gene may influence susceptibility and disease progression.

Purpose of the Study:

• To investigate the association between specific ACE2 gene polymorphisms (rs200180615, rs149039346, rs73635825, and rs140473595) and COVID-19 severity.
• To determine if ACE2 variants correlate with clinical parameters indicative of severe disease.

Main Methods:

• Genotyping of four ACE2 polymorphisms using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).
• Analysis of 84 controls, 80 outpatients, and 168 intensive care unit (ICU) patients with COVID-19.
• Statistical analysis including odds ratios (OR), confidence intervals (CI), and inheritance models.

Main Results:

• No significant association was found for ACE2 polymorphisms rs200180615, rs149039346, and rs73635825.
• The ACE2 rs140473595 CT and TT genotypes were significantly associated with a higher risk of severe COVID-19 in ICU patients compared to controls (OR > 5.8, p < 0.005).
• Mutant allele carriers (CT, TT) showed significant alterations in clinical markers of inflammation and organ damage (CRP, HsTroponin, D-dimer, urea, NEU, LYM) compared to wild-type carriers.

Conclusions:

• The ACE2 rs140473595 polymorphism is a potential genetic marker associated with increased severity of COVID-19.
• Further investigation in diverse ethnic and geographical populations is warranted to validate the role of ACE2 variants in SARS-CoV-2 infection outcomes.