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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.
  • Sabater Molina M; Cardiac Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
  • Nicolás Rocamora E; Cardiogenetic Laboratory, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.
  • Bendicho AI; Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Madrid, Spain.
  • Vázquez EG; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN Guard-Heart), Madrid, Spain.
  • Zorio E; Cardiac Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
  • Rodriguez FD; Microbiology Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
  • Gil Ortuño C; Department of Infectious Disease, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
  • Rodríguez AI; Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Madrid, Spain.
  • Sánchez-López AJ; Cardiology Department, Unidad de Cardiopatías Familiares y Muerte Súbita, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
  • Jara Rubio R; Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Madrid, Spain.
  • Moreno-Docón A; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN Guard-Heart), Madrid, Spain.
  • Marcos PJ; Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
  • García Pavía P; Cardiac Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
  • Villa RB; Cardiogenetic Laboratory, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.
  • Gimeno Blanes JR; Cardiac Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain.
PLoS One ; 17(2): e0263140, 2022.
Article in English | MEDLINE | ID: covidwho-1854993
ABSTRACT

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Severity of Illness Index / Peptidyl-Dipeptidase A / Polymorphism, Single Nucleotide / Receptor, Angiotensin, Type 1 / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2022 Document Type: Article Affiliation country: Journal.pone.0263140

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Severity of Illness Index / Peptidyl-Dipeptidase A / Polymorphism, Single Nucleotide / Receptor, Angiotensin, Type 1 / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Type of study: Prognostic study / Randomized controlled trials Topics: Variants Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2022 Document Type: Article Affiliation country: Journal.pone.0263140