ACE2 K26R single-nucleotide polymorphism and its correlation with the severity of COVID-19 infection

Background: During the SARS-CoV-2 pandemic, the severity of infection has shown marked variability among humans. Genetic polymorphisms in the angiotensin-converting enzyme 2 (ACE2) receptor have been suggested as one of the underlying causes. In this study, we analyzed the genetic polymorphisms in the K26R (rs4646116) hACE2 gene among Egyptian patients with SARS-CoV-2. We aimed to evaluate the role of genetic variations in SARS-CoV-2 infectivity and outcome. Methods: Genotype distributions were assayed by allele discrimination assay utilizing TaqMan probes. The genotype variants were correlated with serum levels of ACE2, laboratory findings, and the severity of infection. Results: K26R genotype analysis revealed that the “CC” genotype was predominant in the control (95.8%) & and patient (78.9%) groups. The “CT” variant was predominant in SARS-CoV-2 (17.6%) with a significant difference from the controls (p 0.05), and “TT” was only present in the diseased group (3.5%). The “T” allele was associated with the lowest serum ACE2 levels, indicating a worse prognosis. The “CT” genotype was predominant in patients with moderate severity, and the “TT” genotype showed the highest chest x-ray score. Elevated CRP, serum creatinine, liver transaminases, and low serum albumin were found in the “CT” genotype. Conclusion: K26R gene variants are correlated with the incidence of SARS-CoV-2 infection severity, with the “T” allele being unique to the patient group and associated with the lowest serum ACE2 levels.