Angiotensin System Polymorphisms’ in SARS-CoV-2 Positive Patients: Assessment Between Symptomatic and Asymptomatic Patients: A Pilot Study

Abstract

Introduction The renin–angiotensin–aldosterone system (RAAS), a metabolic cascade regulating pressure and circulating blood volume, has been considered the main system involved in the pathogenesis of severe lung injury and organs decline in COVID-19 patients. The angiotensin I-converting enzyme ( ACE1 ), angiotensin-converting enzyme 2 ( ACE2 ), angiotensinogen (AGT) and receptors angiotensin II receptor type 1 ( AGTR1 ) are key factors for SARS-CoV-2 entering in the cells, sodium and water retention with an increase blood pressure, promotion of fibrotic and inflammatory phenomena resulting in a cytokine storm. Methods In this pilot study, the frequencies of six polymorphisms in the ACE1, ACE2, AGT and AGTR1 genes were analysed in symptomatic patients affected by COVID-19 and compared with the results obtained from asymptomatic subjects. Results Thus, we have identified that rs2074192 ( ACE2 ), rs1799752 ( ACE1 ) and rs699 ( AGT ) SNPs could potentially be a valuable tool for predicting the clinical outcome of SARS-CoV-2 infected patients. A genetic predisposition may be prospected for severe internal organ damages and poor prognosis in patients with COVID-19 disease, as observed in symptomatic vs asymptomatic. Conclusion This study provides evidence that analysis of RAAS polymorphisms could be considered the key point in understanding and predicting the SARS-CoV-2 course infection.

Severity of coronavirus disease 19: Profile of inflammatory markers and ACE (rs4646994) and ACE2 (rs2285666) gene polymorphisms in Iraqi patients

“…This is due to the fact that the two enzymes have been implicated in causing severe lung injury and organ regression in COVID-19 patients. Besides, their receptors are key factors for the entry of SARS-CoV-2 into cells, retention of sodium and water with hypertension, and the promotion of fibrotic and inflammatory conditions that lead to cytokine release syndrome (or cytokine storm) ( Cafiero et al, 2021 ). Thus, ACE and ACE2 gene expression and polymorphism require extensive research to understand their impact on susceptibility to SARS-CoV-2 infection and disease outcome in COVID-19 patients.…”

“…The ACE2 gene (Gene ID: Gene ID: 59272) is located in the short arm of human X chromosome (Xp22.2) and consists of 22 exons ( https://www.ncbi.nlm.nih.gov/gene/59272 ). Several SNPs of the gene, for instance rs4240157, rs4646155, and rs4830542, have been associated with the risk of hypertension, but recent studies in COVID-19 have focused on SNP rs2285666 ( Cafiero et al, 2021 ; Devaux et al, 2020 ; Gómez et al, 2020 ; Karakaş Çelik et al, 2021 ; Pouladi and Abdolahi, 2021 ; Singh et al, 2021 ). Although these studies proposed a role for SNPs rs4646994 and rs2285666 in COVID-19 susceptibility and/or disease severity, the evidence has not been conclusive as some findings have not been replicated.…”

The Impact of ACE2 Polymorphisms on COVID-19 Disease: Susceptibility, Severity, and Therapy

“…Considering the double effect of sACE2 on hypertension and antiviral activity, this may partly explain the high incidence rate of hypertension (58%) in critically ill patients with COVID-19 (Sulaiman et al, 2021). By the way, ACE2 rs2074192 T allele and rs2285666 G allele, which are listed in the Table 2, have been reported to be associated with more severe clinical outcomes of SARS-CoV-2 infection (Cafiero et al, 2021;Mohlendick et al, 2021). Thus, besides factors such as aging, vascular disorders and delayed virus clearance, variants-mediated risks are worth exploring in more detail.…”

Angiotensin-converting enzyme polymorphisms AND Alzheimer’s disease susceptibility: An updated meta-analysis

“…The I/D genotype is regarded as a determinant of ACE expression levels in plasma, cells and tissues. Approximately 50% variability in plasma levels of ACE depends on the rs1799752 polymorphism [ 9 , 10 ]. Individuals carrying the D allele have higher plasma ACE levels compared to I homozygotes [ 11 ].…”