Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/15243
Título
Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease.
Autor(es)
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
Fecha de publicación
2022
Cita
Sabater Molina M, Nicolás Rocamora E, Bendicho AI, Vázquez EG, Zorio E, Rodriguez FD, Gil Ortuño C, Rodríguez AI, Sánchez-López AJ, Jara Rubio R, Moreno-Docón A, Marcos PJ, García Pavía P, Villa RB, Gimeno Blanes JR. Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease. PLoS One. 2022 Feb 4;17(2):e0263140. doi: 10.1371/journal.pone.0263140. PMID: 35120165; PMCID: PMC8815985.
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Tipo de documento
journal article
Resumen
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.
MESH
Polymorphism, Single Nucleotide | Severity of Illness Index | Aged | Angiotensin-Converting Enzyme 2 | COVID-19 | Female | Genotype | Humans | Male | Middle Aged | Peptidyl-Dipeptidase A | Receptor, Angiotensin, Type 1 | SARS-CoV-2
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