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Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19: A case study.

ABSTRACT: 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.

SUBMITTER: Karakas Celik S

PROVIDER: S-EPMC8426884 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRecent 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).MethodsWe 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.ResultsAnalysis 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.ConclusionsBased 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.

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Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19: A case study.

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