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Due to the unique affinity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the angiotensin-converting enzyme 2 (ACE2) receptor in patients, the foremost recent evidence indicated that ACE1 and ACE2 polymorphisms could affect the susceptibility of individuals to SARS-CoV-2 infection and also the disease outcome. Here, we aimed to assess the possible association between two polymorphisms and the severity of disease in patients. In the present study, 146 patients with COVID-19 who were admitted to the Mazandaran University of Medical Sciences hospitals between March 2020 and July 2020 were enrolled in this case-control study. The patients were divided into four groups based on clinical symptoms and severity of the diseases (mild, moderate, severe, and critical). After DNA extraction, the ACE gene I/D polymorphism (rs4646994) and ACE2 gene polymorphism (rs2285666) were genotyped using Gap-PCR and PCR-RFLP techniques, respectively. Then, five samples from each obtained genotype were confirmed by Sanger sequencing technique. Data were analyzed with SAS software version 9.1 using appropriate statistical procedures. The ACE gene I/D polymorphism (rs4646994) genotypes were classified into three types: I/I, I/D, and D/D. Our finding indicated that the prevalence of ACE1 D/D genotype was significantly higher in severe and critical COVID-19 patients (P = 0.0016). Additionally, the analysis revealed a remarkable association between rs4646994 SNP and the HB and ESRI levels in patients (P < 0.05). Although the ACE2 rs2285666 SNP was not related to the severity of disease, this variant was significantly associated with ALT, ESRI, and P. These results provide preliminary evidence of a genetic association between the ACE-D/D genotype and the D allele of ACE1 genotype and the disease severity. Therefore, our findings might be useful for identifying the susceptible population groups for COVID-19 therapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Recent studies emphasize the significant impact of the renin-angiotensin aldosterone system (RAAS) as a risk factor associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, according to the literature, the effect of rs4646994 and rs2285666 polymorphisms on susceptibility and progression to severe clinical outcomes is still controversial. Our aim was to investigate the effect of polymorphisms such as rs4646994 and rs2285666 on susceptibility to coronavirus disease-2019 (COVID-19)., Methods: We conducted a comprehensive literature search using databases such as ISI Web of Science, PubMed, Scopus, and Google Scholar to retrieve studies on the effect of two polymorphisms (rs4646994 and rs2285666) of the angiotensin-converting enzyme (ACE) gene on COVID-19. Finally, the effect of each polymorphism on SARS-CoV-2 infection was measured based on the odds ratio with 95% confidence intervals., Results: Analysis of the rs4646994 polymorphism showed that the frequency of the D allele in patients infected with COVID-19 was higher than that the I allele. Moreover, the authors found that the DD genotype increased the risk of severe disease by 1.7-fold in Asian population, whereas, this was not the case in the Western population. However, the rs4646994 II genotype plays a protective role against COVID-19 in Western countries. In the case of the rs2285666 polymorphism based on patient ethnicity, the C allele had the highest frequency. Interestingly, in people harboring the GG and TT genotypes, the risk of progression to severe disease significantly increased, while people with genotypes such as GA, AA and CC seem to be more resistant to severe Covid-19., Conclusions: Based on geographical region, the rs4646994 DD genotype may be considered as a predictive biomarker to identify the susceptibility of human to SARS-CoV-2 infection and severe COVID-19 outcomes. We also concluded that individuals with GG and TT genotypes are significantly more susceptible to severe outcomes of disease, while conversely, individuals with GA, AA, and CC genotypes are less susceptible to severe COVID-19., Competing Interests: Declaration of competing interest Formally, we confirm, there are not conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

COVID-19 and the renin-angiotensin system (RAS) are linked by angiotensin-converting enzyme 2 (ACE2), a key enzyme in RAS that has been validated as a SARS-CoV-2 receptor. Functional ACE1/ACE2 gene polymorphisms may lead to the imbalance between ACE/ACE2 ratio and thus generating RAS imbalance that is associated with higher degrees of lung damage in ARDS that may contribute to the COVID-19 infection outcome. Herein, we investigated the role of RAS gene polymorphisms, ACE1 (A2350G) and ACE2 (G8790A) as risk predictors for susceptibility and severity of COVID-19 infection. A total of 129 included: negative controls without a history of COVID-19 infection (n = 50), positive controls with a history of COVID-19 infection who were not hospitalized (n = 35), and patients with severe COVID-19 infection who were hospitalized in the intensive care unit (n = 44). rs4343 of ACE and rs2285666 of ACE2 were genotyped using PCR-RFLP method. Our results indicated that susceptibility to COVID-19 infection was associated with age, GG genotype of A2350G (Pa = 0.01; OR 4.7; 95% CI 1.4-15.1 and Pc = 0.040; OR 2.5; 95% CI 1.05-6.3) and GG genotype of G8790A (Pa = 0.044; OR 6.17; 95% CI 1.05-35.71 and Pc = 0.0001; OR 5.5; 95% CI 2.4-12.4). The G allele of A2350G (Pa = 0.21; OR 1.74; 95% CI 0.73-4.17 and Pc = 0.007; OR 2.1; 95% CI 1.2-3.5) and G allele of G8790A (Pa = 0.002; OR 4.26; 95% CI 1.7-10.65 and Pc = 0.0001; OR 4.7; 95% CI 2.4-9.2) were more frequent in ICU-admitted patients and positive control group. Also lung involvement due to COVID-19 infection was associated with age and the comorbidities such as diabetes. In conclusion, our findings support the association between the wild genotype (GG) of ACE2 and homozygote genotype (GG) of ACE1 and sensitivity to COVID-19 infection, but not its severity. However, confirmation of this hypothesis requires further studies with more participants., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) is an infectious disease, and the reason behind the currently ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme (ACE2) has been recognized as the specific receptor of the SARS-CoV-2 virus. Although the possible effect of ACE2 gene polymorphism remains unknown, human ACE2 receptor expression influences SARS-CoV-2 susceptibility and COVID-19 disease outcome. In this study, we aimed to investigate the relationship between ACE gene I/D polymorphism, ACE2 receptor gene polymorphism, and COVID-19 severity. ACE gene insertion/deletion (I/D) polymorphism and ACE2 receptor gene rs2106809 and rs2285666 polymorphisms were determined using polymerase chain reaction (PCR) and PCR-based restriction fragment length polymorphism methods, respectively, in 155 COVID-19 patients who were divided into three groups (mild, moderate, and severe) according to clinical symptoms. However, the distribution of genotype and allele frequencies of ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not statistically significant in all groups. In conclusion, in the study population, ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not associated with the severity of COVID-19 infection. Although ACE2 receptor gene expression may affect the susceptibility to COVID-19, there is no existing evidence that the ACE or ACE2 gene polymorphisms are directly associated with COVID-19 severity. Interindividual differences in COVID-19 severity might be related to epigenetic mechanisms of ACE2 receptor gene expression or variations in other genes suggested to play a critical role in COVID-19 pathogenesis such as pro-inflammatory cytokines and coagulation indicators., (© 2021 Wiley Periodicals LLC.)

Background/aim: The G8790A (rs2285666) functional polymorphism of the angiotensin-converting enzyme 2 (ACE2) gene influences alternative mRNA splicing and quantitatively affects the enzyme's production. Specifically, the presence of the A allele has been associated with higher ACE2 plasma levels. In this study, we investigated the possible association of the functional polymorphism ACE2-G8790A with the pathogenesis of basal cell carcinoma (BCC)., Patients and Methods: A total of 190 DNA samples were studied, including 91 BCC patients and 99 controls of Greek origin. Molecular genotyping for the ACE2 G8790A polymorphism was carried out by PCR amplification, followed by AluI enzyme digestion and agarose gel electrophoresis of the DNA fragments., Results: The allelic and genotypic frequencies presented no statistical difference between the patient and the control group., Conclusion: There is no association between the ACE2 G8790A polymorphism and pathogenesis of BCC., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)