IFITM3, FURIN, ACE1, and TNF-α Genetic Association With COVID-19 Outcomes: Systematic Review and Meta-Analysis

Araújo, João Locke Ferreira de; Menezes, Diego; Aguiar, Renato Santana; Souza, Renan P.

doi:10.3389/fgene.2022.775246

Cited by 12 publications

(15 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also found the polymorphisms ACE2 rs2285666, ACE2 rs2106809, ACE2 rs2074192, AGTR1 rs5186, and TNFA rs1800629 to be associated with increased risk of developing severe disease manifestations. Recent genome-wide association studies (GWASs) identified association of ACE2 , TMPRSS2 , CCR5 , and APOE variants with susceptibility to SARS-CoV-2 infection ( de Araújo et al, 2022 , Karlsen, 2022 Apr , Baranova et al, 2021 ). However, the studies did not find association with ACE1 , IFITM3 , AGTR1 , and TNFA .…”

Section: Discussionmentioning

confidence: 99%

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Gupta

Kaur²,

Pathak³

et al. 2022

Gene

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Gupta

Kaur²,

Pathak³

et al. 2022

Gene

View full text Add to dashboard Cite

“…On the other hand, genetic variation of a gene likely modifies the function and expression of an encoded product, which could be considered the interindividual differences in susceptibility to several infectious diseases. So far, few studies have shown the roles of angiotensin-converting enzyme 1 (ACE1), ACE2, and transmembrane protease serine 2 (TMPRSS2) gene variants in the COVID-19 severity ( Gorbalenya et al, 2020 ; Hou et al, 2020 ; de Araújo et al, 2022 ; Gintoni et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

The role of ACE1 I/D and ACE2 polymorphism in the outcome of Iranian COVID-19 patients: A case-control study

Faridzadeh

Mahmoudi²,

Ghaffarpour³

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Background: Since the beginning of the pandemic of coronavirus disease 2019 (COVID-19), many countries have experienced a considerable number of COVID-19 cases and deaths. The etiology of a broad spectrum of symptoms is still debated. Host genetic variants might also significantly influence the outcome of the disease. This study aimed to evaluate the association of angiotensin-converting enzyme (ACE1) gene Insertion/Deletion (I/D) polymorphism (rs1799752) and ACE2 gene rs1978124 single nucleotide polymorphism with the COVID-19 severity.Methods: This study was conducted on 470 COVID-19 patients and a control group of 56 healthy individuals across several major cities in Iran. The blood sample and clinical data were collected from the participants, and their ACE1 I/D and ACE2 rs1978124 polymorphisms were determined using polymerase chain reaction and PCR-RFLP, respectively. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and ACE1 were measured in the blood samples.Results: We found that the ACE1 DD genotype frequency was inversely correlated with the risk of intubation (p = 0.017) and mortality in COVID-19 patients (p = 0.049). Even after adjustment, logistic regression demonstrated that this significant inverse association remained constant for the above variables at odds ratios of (OR) = 0.35 and Odds Ratio = 0.49, respectively. Also, in the expired (p = 0.042) and intubated (p = 0.048) groups with II + ID genotypes, the mean level of CRP was significantly higher than in the DD genotype group. Furthermore, in both intubated and expired groups, the mean serum level of ACE1 was higher compared with non-intubated and survived groups with II or II + ID genotypes. The results also indicated that ACE2 rs1978124 TT + CT genotypes in females have a significant positive role in susceptibility to COVID-19; however, in females, the TT + CT genotypes had a protective effect (OR = 0.098) against the severity of COVID-19.Conclusion: These findings suggest that ACE1 I/D and ACE2 rs1978124 polymorphism could potentially influence the outcome of COVID-19 in the Iranian population.

show abstract

“…The reasons for these discrepancies are unclear and similar to the ACE2 rs2285666 polymorphism require further exploration. Interestingly, a recent meta-analysis evaluating several polymorphisms related to COVID-19 outcomes found a significant association between the polymorphism ACE rs4646994 and COVID-19 severity ( 104 ). Results of individual association studies must be considered carefully and discrepancies in the findings may be the result of underpowered sample sizes, therefore replicates and more robust studies should be considered to validate these associations.…”

Section: Discussionmentioning

confidence: 99%

Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population

et al. 2022

View full text Add to dashboard Cite

Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: ACE rs4646994, ACE2 rs2285666, and LZTFL1 rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases (n = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients (n = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism LZTFL1 rs11385942 as an important risk factor for hospitalization (p < 0.01; OR = 5.73; 95% CI = 1.2–26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79–0.93). These results suggest that LZTFL1 rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.

show abstract

IFITM3, FURIN, ACE1, and TNF-α Genetic Association With COVID-19 Outcomes: Systematic Review and Meta-Analysis

Cited by 12 publications

References 65 publications

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

The role of ACE1 I/D and ACE2 polymorphism in the outcome of Iranian COVID-19 patients: A case-control study

Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population

Contact Info

Product

Resources

About