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

Cafiero, Concetta; Rosapepe, Felice; Palmirotta, Raffaele; Re, Agnese; Ottaiano, Maria Pia; Benincasa, Giulio; Perone, Romina; Varriale, Elisa; D’Amato, Gerardo; Cacciamani, Andrea; Micera, Alessandra; Pisconti, Salvatore

doi:10.2147/pgpm.s303666

Cited by 53 publications

(70 citation statements)

References 43 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Susceptibility to coronavirus disease 2019 (COVID-19) and disease severity has recently been associated with inflammatory markers and genetic polymorphisms of ACE (angiotensin-converting enzyme) and ACE2 genes, but the evidence has been inconclusive. This case-control study (99 COVID-19 patients and 96 controls) sought to assess the significance of age, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and SARS-CoV-2 RT-PCR cycle threshold (Ct) in severity of COVID-19. Besides, two variants of ACE and ACE2 genes (rs4646994 and rs2285666, respectively) were analyzed to determine their role in COVID-19 susceptibility and/or disease severity. Results revealed that age, CRP and NLR were significantly elevated in severe cases compared to moderate cases, while RT-PCR Ct value was significantly decreased. Allele and genotypes of both variants were not associated with COVID-19 risk, with the exception of rs2285666 A allele. It showed a significantly higher frequency in female patients than in female controls (probability = 0.041 ) . In conclusion, the study indicated the role of age, CRP, NLR and SARS-CoV-2 RT-PCR Ct in susceptibility to COVID-19 severity. However, analysis of the ACE and ACE2 gene variants (rs4646994 and rs2285666, respectively) showed that the two variants were not associated with the risk of developing COVID-19.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…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.…”

Section: Comorbidities and Ace2 Polymorphismsmentioning

confidence: 99%

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

Chen

Zhang

et al. 2021

Front. Cell. Infect. Microbiol.

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The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has currently spread worldwide, leading to high morbidity and mortality. As the putative receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) is widely distributed in various tissues and organs of the human body. Simultaneously, ACE2 acts as the physiological counterbalance of ACE providing homeostatic regulation of circulating angiotensin II levels. Given that some ACE2 variants are known to cause an increase in the ligand-receptor affinity, their roles in acquisition, progression and severity of COVID-19 disease have aroused widespread concerns. Therefore, we summarized the latest literature and explored how ACE2 variants and epigenetic factors influence an individual’s susceptibility to SARS-CoV-2 infection and disease outcome in aspects of ethnicity, gender and age. Meanwhile, the possible mechanisms for these phenomena were discussed. Notably, recombinant human ACE2 and ACE2-derived peptides may have special benefits for combating SARS-CoV-2 variants and further studies are warranted to confirm their effects in later stages of the disease process. As the uncertainty regarding the severity and transmissibility of disease rises, a more in-depth understanding of the host genetics and functional characteristics of ACE2 variants will not only help explain individual clinical differences of the disease, but also contribute to providing effective measures to develop solutions and manage future outbreaks of SARS-CoV-2.

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“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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Background Many studies among different ethnic populations suggested that angiotensin converting enzyme (ACE) gene polymorphisms were associated with susceptibility to Alzheimer’s disease (AD). However, the results remained inconclusive. In the present meta-analysis, we aimed to clarify the effect of ACE polymorphisms on AD risk using all available relevant data. Methods Systemic literature searches were performed using PubMed, Embase, Alzgene and China National Knowledge Infrastructure (CNKI). Relevant data were abstracted according to predefined criteria. Results Totally, 82 independent cohorts from 65 studies were included, focusing on five candidate polymorphisms. For rs1799752 polymorphism, in overall analyses, the insertion (I) allele conferred increased risk to AD compared to the deletion (D) allele (I vs. D: OR = 1.091, 95% CI = 1.007–1.181, p = 0.032); while the I carriers showed increased AD susceptibility compared with the D homozygotes (II + ID vs. DD: OR = 1.131, 95% CI = 1.008–1.270, p = 0.036). However, none of the positive results passed FDR adjustment. In subgroup analysis restricted to late-onset individuals, the associations between rs1799752 polymorphism and AD risk were identified using allelic comparison (OR = 1.154, 95% CI = 1.028–1.295, p = 0.015, FDR = 0.020), homozygotes comparison, dominant model and recessive model (II vs. ID + DD: OR = 1.272, 95% CI = 1.120–1.444, p < 0.001, FDR < 0.001). Nevertheless, no significant association could be revealed after excluding studies not in accordance with Hardy-Weinberg equilibrium (HWE). In North Europeans, but not in East Asians, the I allele demonstrated increased AD susceptibility compared to the D allele (OR = 1.096, 95% CI = 1.021–1.178, p = 0.012, FDR = 0.039). After excluding HWE-deviated cohorts, significant associations were also revealed under homozygotes comparison, additive model (ID vs. DD: OR = 1.266, 95% CI = 1.045–1.534, p = 0.016, FDR = 0.024) and dominant model (II + ID vs. DD: OR = 1.197, 95% CI = 1.062–1.350, p = 0.003, FDR = 0.018) in North Europeans. With regard to rs1800764 polymorphism, significant associations were identified particularly in subgroup of European descent under allelic comparison (T vs. C: OR = 1.063, 95% CI = 1.008–1.120, p = 0.023, FDR = 0.046), additive model and dominant model (TT + TC vs. CC: OR = 1.116, 95% CI = 1.018–1.222, p = 0.019, FDR = 0.046). But after excluding studies not satisfying HWE, all these associations disappeared. No significant associations were detected for rs4343, rs4291 and rs4309 polymorphisms in any genetic model. Conclusions Our results suggested the significant but modest associations between rs1799752 polymorphism and risk to AD in North Europeans. While rs4343, rs4291 and rs4309 polymorphisms are unlikely to be major factors in AD development in our research.

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

Cited by 53 publications

References 43 publications

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

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

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

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

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