AUTHOR=Martínez-Gómez Laura E. , Herrera-López Brígida , Martinez-Armenta Carlos , Ortega-Peña Silvestre , Camacho-Rea María del Carmen , Suarez-Ahedo Carlos , Vázquez-Cárdenas Paola , Vargas-Alarcón Gilberto , Rojas-Velasco Gustavo , Fragoso José Manuel , Vidal-Vázquez Patricia , Ramírez-Hinojosa Juan P. , Rodríguez-Sánchez Yunuen , Barrón-Díaz David , Moreno Mariana L. , Martínez-Ruiz Felipe de J. , Zayago-Angeles Dulce M. , Mata-Miranda Mónica Maribel , Vázquez-Zapién Gustavo Jesús , Martínez-Cuazitl Adriana , Barajas-Galicia Edith , Bustamante-Silva Ludwing , Zazueta-Arroyo Diana , Rodríguez-Pérez José Manuel , Hernández-González Olivia , Coronado-Zarco Roberto , Lucas-Tenorio Vania , Franco-Cendejas Rafael , López-Jácome Luis Esau , Vázquez-Juárez Rocío Carmen , Magaña Jonathan J. , Cruz-Ramos Marlid , Granados Julio , Hernández-Doño Susana , Delgado-Saldivar Diego , Ramos-Tavera Luis , Coronado-Zarco Irma , Guajardo-Salinas Gustavo , Muñoz-Valle José Francisco , Pineda Carlos , Martínez-Nava Gabriela Angélica , López-Reyes Alberto TITLE=ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.812940 DOI=10.3389/fimmu.2022.812940 ISSN=1664-3224 ABSTRACT=

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.