APOE e4 Genotype Predicts Severe COVID-19 in the UK Biobank Community Cohort

Kuo, Chia Ling; Pilling, Luke C.; Atkins, Janice L.; Masoli, Jane; Delgado, João; Kuchel, George A.; Melzer, David

doi:10.1093/gerona/glaa131

Cited by 313 publications

(272 citation statements)

References 10 publications

Supporting

Mentioning

250

Contrasting

Unclassified

Order By: Relevance

“…APOE is a gene that encodes a lipid binding protein involved in cholesterol metabolism 56 . Preliminary evidence suggests that the e4 allele of APOE may lead to a higher risk of deep vein thrombosis and the same allele also predicts severe COVID-19 57,58 . F2 and F4 are both involved in the formation of a fibrin clot (Reactome:R-HSA-140877).…”

Section: Discussion and Summarymentioning

confidence: 99%

Investigation of COVID-19 comorbidities reveals genes and pathways coincident with the SARS-CoV-2 viral disease

Dolan

Hill

Mukherjee

et al. 2020

Preprint

View full text Add to dashboard Cite

The emergence of the SARS-CoV-2 virus and subsequent COVID-19 pandemic initiated intense research into the mechanisms of action for this virus. It was quickly noted that COVID-19 presents more seriously in conjunction with other human disease conditions such as hypertension, diabetes, and lung diseases. We conducted a bioinformatics analysis of COVID-19 comorbidity-associated gene sets, identifying genes and pathways shared among the comorbidities, and evaluated current knowledge about these genes and pathways as related to current information about SARS-CoV-2 infection. We performed our analysis using GeneWeaver (GW), Reactome, and several biomedical ontologies to represent and compare common COVID-19 comorbidities. Phenotypic analysis of shared genes revealed significant enrichment for immune system phenotypes and for cardiovascular-related phenotypes, which might point to alleles and phenotypes in mouse models that could be evaluated for clues to COVID-19 severity. Through pathway analysis, we identified enriched pathways shared by comorbidity datasets and datasets associated with SARS-CoV-2 infection.

show abstract

Section: Discussion and Summarymentioning

confidence: 99%

Investigation of COVID-19 comorbidities reveals genes and pathways coincident with the SARS-CoV-2 viral disease

Dolan

Hill

Mukherjee

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Coronavirus disease 2019 (COVID-19) is a contagious disease; therefore, its prevalence (per 10 6 people), casefatality (per 100 infected cases), and mortality (per 10 6 people) may be affected by various social factors, such as the life expectancy at birth, country income, etc. Very recently some investigators suggested that some genetic polymorphisms might be involved in susceptibility to genetic polymorphisms or outcome of the disease [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…Considering that GSTP1 is involved in cellular detoxification and it has important role in lung function, it is suggested that GSTP1 plays an important role in susceptibility to SARS-CoV-2 infection and/or its outcome. Very recently, association between some genetic polymorphisms and morbidity/mortality of COVID-19 were reported [12][13][14][15][16]. A study showed that the COVID-19 mortality and case-fatality are associated with the GSTT1 polymorphism [12].…”

Section: Introductionmentioning

confidence: 99%

The morbidity and mortality of COVID-19 are correlated with the Ile105Val glutathione S-transferase P1 polymorphism

Saadat

2020

Egypt J Med Hum Genet

View full text Add to dashboard Cite

Background Oxidative stress is an important issue in coronavirus disease 2019 (COVID-19). Considering that glutathione S-transferase P1 (GSTP1) is involved in cellular detoxification, it may play an important role in susceptibility to infection with SARS-CoV-2 and/or its outcome. In the present study, the association between the Ile105Val GSTP1 polymorphism (rs1695) and susceptibility to SARS-CoV-2 infection, as well as its outcome was investigated. Data on the prevalence (per 106 people), case-fatality (per 100 infected cases), and mortality (per 106 people) of COVID-19 and various potential confounders (the life expectancy at birth, density of medical doctors, density of nursing and midwifery personnel, and the gross national income per capita) were used. The latest data available for 45 countries were used for the study. Results In multivariate linear regression analyses, the Val105 allelic frequency showed positive association with the log-prevalence (partial r = 0.308, p = 0.042) and log-mortality of COVID-19 (partial r = 0.316, p = 0.037). The log-fatality did not show association with the allelic frequency. In the next step, only countries with the gross national income per capita more than $15,000 were included in the analysis. In the selected countries, the frequency of Val105 was positively associated with the log-prevalence (partial r = 0.456, p = 0.009) and log-mortality of COVID-19 (partial r = 0.544, p = 0.001). Conclusions The present findings indicate that countries with higher Val105 allelic frequency of the rs1695 polymorphism showed higher prevalence and mortality of COVID-19.

show abstract

“…Disruption of the kallikrein-kinin system is identified in cardiovascular diseases, chronic kidney diseases, and Alzheimer disease (Kayashima et al, 2012;Ji et al, 2019) and each of these conditions can increase the susceptibility to SARS-CoV-2 (Ji et al, 2020;Kuo et al, 2020). SARS-CoV-induced loss of ACE2 (Kuba et al, 2005) reduces ACE2-dependent degradation of des-Arg 9 -bradykinin (Sodhi et al, 2018) and activates this pathway (Figure 7).…”

Section: Sars-cov-2 and The Kallikrein-kinin Systemmentioning

confidence: 99%

COVID-19 Usurps Host Regulatory Networks

2020

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the cell surface and this complex is internalized. ACE2 serves as an endogenous inhibitor of inflammatory signals associated with four major regulator systems: the renin-angiotensin-aldosterone system (RAAS), the complement system, the coagulation cascade, and the kallikrein-kinin system (KKS). Understanding the pathophysiological effects of SARS-CoV-2 on these pathways is needed, particularly given the current lack of proven, effective treatments. The vasoconstrictive, prothrombotic and pro-inflammatory conditions induced by SARS-CoV-2 can be ascribed, at least in part, to the activation of these intersecting physiological networks. Moreover, patients with immune deficiencies, hypertension, diabetes, coronary heart disease, and kidney disease often have altered activation of these pathways, either due to underlying disease or to medications, and may be more susceptible to SARS-CoV-2 infection. Certain characteristic COVID-associated skin, sensory, and central nervous system manifestations may also be linked to viral activation of the RAAS, complement, coagulation, and KKS pathways. Pharmacological interventions that target molecules along these pathways may be useful in mitigating symptoms and preventing organ or tissue damage. While effective anti-viral therapies are critically needed, further study of these pathways may identify effective adjunctive treatments and patients most likely to benefit.

show abstract

APOE e4 Genotype Predicts Severe COVID-19 in the UK Biobank Community Cohort

Cited by 313 publications

References 10 publications

Investigation of COVID-19 comorbidities reveals genes and pathways coincident with the SARS-CoV-2 viral disease

Investigation of COVID-19 comorbidities reveals genes and pathways coincident with the SARS-CoV-2 viral disease

The morbidity and mortality of COVID-19 are correlated with the Ile105Val glutathione S-transferase P1 polymorphism

COVID-19 Usurps Host Regulatory Networks

Contact Info

Product

Resources

About