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

Abstract

Objective:

An epidemic of acute pneumonia caused by SARS-CoV-2 spread rapidly worldwide in December 2019. The first interaction between the virus and the host cell occurs via the binding of the spike (S) protein to the ACE2 receptor. ACE2 gene expression correlates with COVID-19 severity, and certain polymorphisms may alter expression or susceptibility.

Methods:

This study investigated ACE2 rs200180615, rs149039346, rs73635825, and rs140473595 polymorphisms by PCR-RFLP. The sample included 84 controls, 80 outpatients, and 168 intensive care unit (ICU) patients.

Results:

No significant associations were found for rs200180615, rs149039346, or rs73635825. In contrast, compared with controls, ICU patients carrying the rs140473595 CT genotype (OR = 7.222, 95% CI: 3.563–14.639, p < 0.000) or TT genotype (OR = 5.893, 95% CI: 1.578–22.000, p = 0.005) had a markedly higher risk of severe disease. Inheritance model analysis also revealed significant associations for the dominant (CC vs. CT/TT; OR = 2.37, 95% CI: 1.38–4.05) and co-dominant (CC vs. TC; OR = 2.37, 95% CI: 1.37–4.09) models. Clinical parameters including CRP, HsTroponin, D-dimer, urea, NEU, and LYM were associated with COVID-19 severity. Independent t-test analysis showed that mutant allele carriers (CT, TT) had significant alterations in these parameters compared with the wild-type CC genotype, consistent with trends observed as disease severity increased.

Conclusion:

The ACE2 rs140473595 polymorphism is associated with COVID-19 severity. Broader studies in diverse populations are needed to further clarify the role of ACE2 variants in disease progression.