Alu retrotransposons and COVID-19 susceptibility and morbidity

Li, Manci; Schifanella, Luca; Larsen, Peter A.

doi:10.1186/s40246-020-00299-9

Cited by 19 publications

(33 citation statements)

References 87 publications

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“…Also, high levels and activity of ACE would further increase the activity of the AngII/AT1R pathway. Moreover, advanced age, cardiovascular diseases, hypertension and metabolic diseases such as type 2 diabetes and obesity also lead to further dysfunctions in the renin-angiotensin-aldosterone system (RAAS), likely rendering patients with these underlying comorbidities more susceptible to further repercussions of ACE/ACE2 imbalance ( 7 – 9 ) and references therein].…”

Section: Introductionmentioning

confidence: 99%

“…More specifically, the DD genotype of the ACE I/D polymorphism has been associated to higher levels of serum ACE and higher levels of circulating IL6 in patients with myocardial infarction. In contrast, the II genotype has been associated to lower circulating ACE levels, and robust coagulation, and/or enhanced fibrinolysis ( 7 ). Since some of these processes have been reported to be involved in the pathogenesis of COVID-19, the DD genotype could predispose to complications of COVID-19 due to higher baseline ACE levels and its consequences ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the II genotype has been associated to lower circulating ACE levels, and robust coagulation, and/or enhanced fibrinolysis ( 7 ). Since some of these processes have been reported to be involved in the pathogenesis of COVID-19, the DD genotype could predispose to complications of COVID-19 due to higher baseline ACE levels and its consequences ( 7 ). Indeed, an association of the DD genotype of the ACE I/D polymorphism with severe COVID-19 has been reported in hypertensive males ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

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ACE Gene Variants Rise the Risk of Severe COVID-19 in Patients With Hypertension, Dyslipidemia or Diabetes: A Spanish Pilot Study

et al. 2021

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Coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to scale and threaten human health and public safety. It is essential to identify those risk factors that lead to a poor prognosis of the disease. A predisposing host genetic background could be one of these factors that explain the interindividual variability to COVID-19 severity. Thus, we have studied whether the rs4341 and rs4343 polymorphisms of the angiotensin converting enzyme (ACE) gene, key regulator of the renin-aldosterone-angiotensin system (RAAS), could explain the different outcomes of 128 COVID-19 patients with diverse degree of severity (33 asymptomatic or mildly symptomatic, 66 hospitalized in the general ward, and 29 admitted to the ICU). We found that G allele of rs4341 and rs4343 was associated with severe COVID-19 in hypertensive patients, independently of gender (p<0.05). G-carrier genotypes of both polymorphisms were also associated with higher mortality (p< 0.05) and higher severity of COVID-19 in dyslipidemic (p<0.05) and type 2 diabetic patients (p< 0.01). The association of G alleles with disease severity was adjusted for age, sex, BMI and number of comorbidities, suggesting that both the metabolic comorbidities and the G allele act synergistically on COVID-19 outcome. Although we did not find a direct association between serum ACE levels and COVID-19 severity, we found higher levels of ACE in the serum of patients with the GG genotype of rs4341 and rs4343 (p<0.05), what could explain the higher susceptibility to develop severe forms of the disease in patients with the GG genotype, in addition to hypertension and dyslipidemia. In conclusion, our preliminary study suggests that the G-containing genotypes of rs4341 and rs4343 confer an additional risk of adverse COVID-19 prognosis. Thus, rs4341 and rs4343 polymorphisms of ACE could be predictive markers of severity of COVID-19 in those patients with hypertension, dyslipidemia or diabetes. The knowledge of these genetic data could contribute to precision management of SARS-CoV-2 infected patients when admitted to hospital.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ACE Gene Variants Rise the Risk of Severe COVID-19 in Patients With Hypertension, Dyslipidemia or Diabetes: A Spanish Pilot Study

et al. 2021

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“…Among many Alu elements, the ACE1 polymorphism is a good example of how much research has been done thus far. Despite the fact that the Alu is an intron insertion, it can affect gene expression through several mechanisms, including both genetic and epigenetic pathways [60]. At the molecular level, it has also been reported that the presence of the Alu element within intron 16 probably affects the promoter activity of ACE1, which acts as a transacting repressor for RNA polymerase II activity [61,62].…”

Section: Possible Involvement Of Polymorphic Alu Elements and Their Functional Aspectsmentioning

confidence: 99%

Angiotensin–Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms

Yamamoto

Nishida

Yamamoto³

et al. 2021

Genes

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The renin–angiotensin–aldosterone system (RAAS) appears to play an important role in SARS-CoV-2 infection. Polymorphisms within the genes that control this enzymatic system are candidates for elucidating the pathogenesis of COVID-19, since COVID-19 is not only a pulmonary disease but also affects many organs and systems throughout the body in multiple ways. Most striking is the fact that ACE2, one of the major components of the RAAS, is a prerequisite for SARS-COV-2 infection. Recently, we and other groups reported an association between a polymorphism of the ACE1 gene (a homolog of ACE2) and the phenotypic expression of COVID-19, particularly in its severity. The ethnic difference in ACE1 insertion (I)/deletion (D) polymorphism seems to explain the apparent difference in mortality between the West and East Asia. The purpose of this review was to further evaluate the evidence linking ACE1 polymorphisms to COVID-19. We searched the Medline database (2019–2021) for reference citations of relevant articles and selected studies on the clinical outcome of COVID-19 related to ACE1 I/D polymorphism. Although the numbers of patients are not large enough yet, most available evidence supports the notion that the DD genotype adversely influences COVID-19 symptoms. Surprisingly, small studies conducted in several countries yielded opposite results, suggesting that the ACE1 II genotype is a risk factor. This contradictory result may be the case in certain geographic areas, especially in subgroups of patients. It may also be due to interactions with other genes or to yet unexplained biochemical mechanisms. According to our hypothesis, such candidates are genes that are functionally involved in the pathophysiology of COVID-19, can act in concert with the ACE1 DD genotype, and that show differences in their frequency between the West and East Asia. For this, we conducted research focusing on Alu-related genes. The current study on the ACE1 genotype will provide potentially new clues to the pathogenesis, treatment, and diagnosis of SARS-CoV-2 infections.

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“…And the disease transmission eventually contributed to a pneumonia epidemic outbreak in 2003. 4 , 5 ACE2 receptor is highly expressed in multiple organ systems 6 and plays an essential negative role in the ACE‐angiotensin II (Ang II)‐angiotensin II receptor type 1 (AT1R) pathway called the classical renin‐angiotensin‐aldosterone system (RAAS) axis, whose positive effect can increase sympathetic nervous system tension. 7 …”

Section: Introductionmentioning

confidence: 99%

Cardiac biomarkers, cardiac injury, and comorbidities associated with severe illness and mortality in coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

Zhu

Wang

et al. 2021

Immunity Inflam & Disease

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Aims To explore the correlation between cardiac‐related comorbidities, cardiac biomarkers, acute myocardial injury, and severity level, outcomes in COVID‐19 patients. Method Pubmed, Web of Science, Embase, CNKI, VIP, Wanfang, Cochrane Library databases, medRxiv, and Sinomed were reviewed systemically. Various types of clinical research reporting cardiac‐related comorbidities, cardiac biomarkers including lactate dehydrogenase (LDH), troponin I (TnI), high sensitivity troponin I (hs‐TnI), creatine kinase (CK), creatine kinase–MB (CK‐MB), myoglobin (Myo), N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) and acute cardiac injury grouped by severity of COVID‐19 were included. Outcome measures were events and total sample size for comorbidities, acute cardiac injury, and laboratory parameters of these biomarkers. The study was performed with Stata version 15.1. Results Seventy studies, with a total of 15,354 cases were identified. The results showed that COVID‐19's severity was related to cardiovascular disease. Similar odds ratios (ORs) were achieved in hypertension except for severe versus critical group (OR = 1.406; 95% CI, 0.942–2.097; p = .095). The relative risk (RR) of acute cardiac injury is 7.01 (95% CI, 5.64–8.71) in non‐survivor cases. When compared with the different severity of cardiac biomarkers, the pool OR of CK, CK‐MB, TnI, Myo and LDH were 2.683 (95% CI, 0.83–8.671; p = .106; I 2 = 0%), 2.263 (95% CI, 0.939–5.457; p = .069), 1.242 (95% CI, 0.628–2.457; p = .534), 1.756 (95% CI, 0.608–5.071; p = .298; I 2 = 42.3%), 1.387 (95% CI, 0.707–2.721; p = .341; I 2 = 0%) in the critical versus severe group, whose trends were not similar to other groups. The standard mean differences (SMD) of CK and TnI in the critical versus severe group were 0.09 (95% CI, −0.33 to 0.50; p = .685; I 2 = 65.2%), 0.478 (95% CI, −0.183 to 1.138; p = .156; I 2 = 76.7%), which means no difference was observed in the serum level of these indicators. Conclusion Most of the findings clearly indicate that hypertension, cardiovascular disease, acute cardiac injury, and related laboratory indicators are associated with the severity of COVID‐19. What is now needed are cross‐national prospectively designed observational or clinical trials that will help improve the certainty of the available evidence and treatment decisions for patients.

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Alu retrotransposons and COVID-19 susceptibility and morbidity

Cited by 19 publications

References 87 publications

ACE Gene Variants Rise the Risk of Severe COVID-19 in Patients With Hypertension, Dyslipidemia or Diabetes: A Spanish Pilot Study

ACE Gene Variants Rise the Risk of Severe COVID-19 in Patients With Hypertension, Dyslipidemia or Diabetes: A Spanish Pilot Study

Angiotensin–Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms

Cardiac biomarkers, cardiac injury, and comorbidities associated with severe illness and mortality in coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

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