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

Sabater Molina, Maria ; Nicolás Rocamora, Elisa ; Bendicho, Asunción Iborra ; Vázquez, Elisa García ; Zorio, Esther ; Rodriguez, Fernando Domínguez ; Gil Ortuño, Cristina ; Rodríguez, Ana Isabel ; Sánchez-López, Antonio J ; Jara Rubio, Rubén ; Moreno-Docón, Antonio ; Marcos, Pedro J ; García Pavía, Pablo ; Villa, Roberto Barriales ; Gimeno Blanes, Juan R Ciccacci, Cinzia

PloS one, 2022-02, Vol.17 (2), p.e0263140-e0263140 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease
Autor: Sabater Molina, Maria ; Nicolás Rocamora, Elisa ; Bendicho, Asunción Iborra ; Vázquez, Elisa García ; Zorio, Esther ; Rodriguez, Fernando Domínguez ; Gil Ortuño, Cristina ; Rodríguez, Ana Isabel ; Sánchez-López, Antonio J ; Jara Rubio, Rubén ; Moreno-Docón, Antonio ; Marcos, Pedro J ; García Pavía, Pablo ; Villa, Roberto Barriales ; Gimeno Blanes, Juan R
Ciccacci, Cinzia
Assuntos: ACE2 ; Aged ; Analysis ; Angiotensin ; Angiotensin converting enzyme ; Angiotensin-converting enzyme 2 ; Angiotensin-Converting Enzyme 2 - genetics ; Annealing ; Biobanks ; Biology and Life Sciences ; Cardiology ; Comorbidity ; Coronaviruses ; COVID-19 ; COVID-19 - genetics ; COVID-19 - pathology ; COVID-19 - virology ; Diabetes mellitus ; Disease susceptibility ; Disease transmission ; Endocrine system ; Female ; Gender ; Genes ; Genetic aspects ; Genetic polymorphisms ; Genetic research ; Genetic variance ; Genotype ; Genotypes ; Health aspects ; Heart ; Heredity ; Humans ; Hypertension ; Infection ; Infections ; Inflammation ; Inflammatory response ; Laboratories ; Lung cancer ; Lung diseases ; Male ; Medicine and Health Sciences ; Middle Aged ; Mortality ; Nucleotides ; Patients ; Peptidyl-Dipeptidase A - genetics ; Physiological aspects ; Polymorphism ; Polymorphism, Single Nucleotide ; Receptor, Angiotensin, Type 1 - genetics ; Renin ; Risk ; SARS-CoV-2 - genetics ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Severity of Illness Index ; Signs and symptoms ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Viral diseases ; Viral infections ; Viruses
É parte de: PloS one, 2022-02, Vol.17 (2), p.e0263140-e0263140
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Competing Interests: The authors have declared that no competing interests exist.
Descrição: 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. 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. 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. 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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

United States: Public Library of Science

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