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

Çelik, Sevim; Genç, Güneş Çakmak; Pişkin, Nihal; Açıkgöz, Bilgehan; Altınsoy, Bülent; İşsiz, Başak Kurucu; Dursun, Ahmet

doi:10.1002/jmv.27160

Cited by 80 publications

(95 citation statements)

References 33 publications

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“…Conversely, our results showed no significant association of this variant with COVID-19 outcomes, but we found a significant association with hypertension that could be an indirect effect of COVID-19 complications (see Supplementary Material ). In agreement with our results, Karakas et al reported that I/D was not associated with the severity of COVID-19 infection in Turkey populations ( 33 ). Nevertheless, it is important to point out that the D/D genotype of ACE gene has a role on the renin–angiotensin system, by increasing ACE levels and angiotensin-inactivating AT-1 receptor, and downstream pathophysiological effects.…”

Section: Discussionsupporting

confidence: 93%

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01–3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01–3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10–2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

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Section: Discussionsupporting

confidence: 93%

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men

et al. 2022

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“…32%; p = 0.049) ( Gómez et al, 2020 ). The two polymorphisms were also not associated with COVID-19 severity in Turkish patients ( Karakaş Çelik et al, 2021 ). However, frequency of rs4646994 II genotype was reported to be significantly increased in Czech patients with symptomatic COVID-19 compared to controls (26.2 vs .…”

Section: Discussionmentioning

confidence: 95%

“…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%

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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“…Recently, controversial results have been published on the role of different ACE2 SNPs in COVID-19 disease. Karakaş et al (2021) failed to show any association between rs2106809 and rs2285666 and the clinical course of COVID-19 in a cohort of 155 patients [35]. On the other hand, Srivastava et al (2020) published a positive correlation between rs2285666 and a lower infection rate as well as case-fatality rate among Indian populations [19].…”

Section: Plos Onementioning

confidence: 99%

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease

et al. 2022

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Background Infection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus. Methods 318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed. Results Four SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12–0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14–0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12–115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26–125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (p<0.05), which might be due to the association with the disease. No association between COVID-19 disease and the different AGTR1 SNPs was evidenced on multivariable, nevertheless the A/A genotype for rs5183 showed an higher hospitalization risk in patients with comorbidities. Conclusions Different genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.

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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

Cited by 80 publications

References 33 publications

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men

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

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease

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