Association between angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin-II receptor 1 (AGTR1) polymorphisms and COVID-19 infection in the southeast of Iran: a preliminary case-control study

Kouhpayeh, H R; Tabasi, Farhad; Dehvari, Mohammad; Naderi, Mohammad; Bahari, Gholamreza; Khalili, Tahereh; Clark, Courtney; Ghavami, Saeid; Taheri, Mohsen

doi:10.1186/s41231-021-00106-0

Cited by 38 publications

(31 citation statements)

References 58 publications

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“…This study shows that comorbidities, older age and male gender were correlated with poor outcome in COVID-19 disease, as it has been previously reported [27]. Recently, Kouhpayeh HR et al (2021) showed a significantly higher age and prevalence of diabetes and hypertension in COVID-19 patients with severe disease than a non-severe disease [28].…”

Section: Discussionsupporting

confidence: 81%

“…In addition, when we analyzed the four severity groups independently, it was remarkable the association of the D/D with the deceased group. According with this, Delanghe et al (2020) reported the COVID-19-associated mortality correlated with D-allele of ACE [46] and the I allele decreased the risk of COVID-19 infection in other cohort of 504 subjects [28]. D/I polymorphism in ACE was also associated with ACE2 protein levels in lung tissue, thereby potentially affecting infectivity by SARS-CoV-2 [47].…”

Section: Plos Onementioning

confidence: 95%

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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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Section: Discussionsupporting

confidence: 81%

Section: Plos Onementioning

confidence: 95%

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

et al. 2022

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“…ITIH3 has been indicated as one of the plasma mortality markers for COVID-19 (Demichev et al, 2020; Völlmy et al, 2021). Angiotensinogen (AGT), is a hormone precursor involved in blood pressure regulation cascade that is implicated as potential biomarker and linked to severity of COVID-19 (Kouhpayeh et al, 2021; Sriram & Insel, 2020). VTN levels, from platelets, were observed to be high in case of SARS-CoV pneumonia as well (Lazzaroni et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality

Budhraja

Basu

Gheware

et al. 2021

Preprint

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The precise molecular mechanisms behind severe life-threatening lung abnormalities during severe SARS-CoV-2 infections are still unclear. To address this challenge, we performed whole transcriptome sequencing of lung autopsies from 31 patients suffering from severe COVID-19 related complications and 10 uninfected controls. Using a metatranscriptome analysis of lung tissue samples we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant “classical” signature (n=23) showed upregulation of unfolded protein response, steroid biosynthesis and complement activation supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) potentially representing “Cytokine Release Syndrome” (CRS) showed upregulation of IL1 cytokines such CCL19 but absence of complement activation and muted inflammation. Further, dissecting expression of individual genes within enriched pathways for patient signature suggests heterogeneity in host response to the primary infection. We found that the majority of patients cleared the SARS-CoV-2 infection, but all suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Gordonia bronchialis in “classical” patients and Staphylococcus warneri in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients that can be identified through the status of the complement activation, presence of specific cytokines and characteristic microbiome. This information can be used to design personalized therapy to treat COVID-19 related complications corresponding to patient signature such as using the identified drug molecules or mitigating specific secondary infections.

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“…The SARS-CoV-2-infected receptor ACE2 is an important member of the RAS system. Any changes in expression and function of the RAS element caused by genetic variation can lead to differences in susceptibility and severity to COVID-19 65 , highlighting the importance of AGT in COVID-19. Cafiero et al 66 studied the genotype and allele frequency distributions of AGT rs699 and found that asymptomatic patients have a lower frequency of the T/C genotype compared to symptomatic patients with COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Potential Genes Associated with COVID-19 and Comorbidity

Feng¹,

Song²,

Guo³

et al. 2022

Int. J. Med. Sci.

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Hypertension, diabetes mellitus, and coronary artery disease are common comorbidities and dangerous factors for infection and serious COVID-19. Polymorphisms in genes associated with comorbidities may help observe susceptibility and disease severity variation. However, specific genetic factors and the extent to which they can explain variation in susceptibility of severity are unclear. Therefore, we evaluated candidate genes associated with COVID-19 and hypertension, diabetes mellitus, and coronary artery disease. In particular, we performed searches against OMIM, NCBI, and other databases, protein-protein interaction network construction, and GO and KEGG pathway enrichment analyses. Results showed that the associated overlapping genes were TLR4, NLRP3, MBL2, IL6, IL1RN, IL1B, CX3CR1, CCR5, AGT, ACE, and F2. GO and KEGG analyses yielded 302 GO terms (q < 0.05) and 29 signaling pathways (q < 0.05), respectively, mainly including coronavirus disease-COVID-19 and cytokine-cytokine receptor interaction. IL6 and AGT were central in the PPI, with 8 and 5 connections, respectively. In this study, we identified 11 genes associated with both COVID-19 and three comorbidities that may contribute to infection and disease severity. The key genes IL6 and AGT are involved in regulating immune response, cytokine activity, and viral infection. Therefore, RAAS inhibitors, AGT antisense nucleotides, cytokine inhibitors, vitamin D, fenofibrate, and vaccines regulating non-immune and immune factors could be potential strategies to prevent and cure COVID-19. The study provides a basis for further investigation of genes and pathways with predictive value for the risk of infection and prognosis and could help guide drug and vaccine development to improve treatment efficacy and the development of personalised treatments, especially for COVID-19 individuals with common comorbidities.

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Association between angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin-II receptor 1 (AGTR1) polymorphisms and COVID-19 infection in the southeast of Iran: a preliminary case-control study

Cited by 38 publications

References 58 publications

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

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

Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality

Potential Genes Associated with COVID-19 and Comorbidity

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