Frontiers in Immunology (Feb 2022)

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men

  • Laura E. Martínez-Gómez,
  • Brígida Herrera-López,
  • Carlos Martinez-Armenta,
  • Silvestre Ortega-Peña,
  • María del Carmen Camacho-Rea,
  • Carlos Suarez-Ahedo,
  • Paola Vázquez-Cárdenas,
  • Gilberto Vargas-Alarcón,
  • Gustavo Rojas-Velasco,
  • José Manuel Fragoso,
  • Patricia Vidal-Vázquez,
  • Juan P. Ramírez-Hinojosa,
  • Yunuen Rodríguez-Sánchez,
  • David Barrón-Díaz,
  • Mariana L. Moreno,
  • Felipe de J. Martínez-Ruiz,
  • Dulce M. Zayago-Angeles,
  • Mónica Maribel Mata-Miranda,
  • Gustavo Jesús Vázquez-Zapién,
  • Adriana Martínez-Cuazitl,
  • Edith Barajas-Galicia,
  • Ludwing Bustamante-Silva,
  • Diana Zazueta-Arroyo,
  • José Manuel Rodríguez-Pérez,
  • Olivia Hernández-González,
  • Roberto Coronado-Zarco,
  • Vania Lucas-Tenorio,
  • Rafael Franco-Cendejas,
  • Luis Esau López-Jácome,
  • Rocío Carmen Vázquez-Juárez,
  • Jonathan J. Magaña,
  • Marlid Cruz-Ramos,
  • Julio Granados,
  • Susana Hernández-Doño,
  • Diego Delgado-Saldivar,
  • Luis Ramos-Tavera,
  • Irma Coronado-Zarco,
  • Gustavo Guajardo-Salinas,
  • José Francisco Muñoz-Valle,
  • Carlos Pineda,
  • Gabriela Angélica Martínez-Nava,
  • Alberto López-Reyes

DOI
https://doi.org/10.3389/fimmu.2022.812940
Journal volume & issue
Vol. 13

Abstract

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01–3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01–3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10–2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

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