Polymorphisms in ACE1, TMPRSS2, IFIH1, IFNAR2, and TYK2 genes are associated with worse clinical outcomes in COVID-19

• Autor(a) principal: Dieter, Cristine
• Data de Publicação: 2023
• Outros Autores: Brondani, Letícia de Almeida, Lemos, Natália Emerim, Schaeffer, Ariell Freires, Boeckel, Caroline Zanotto de, Ramos, Denise Taurino, Girardi, Eliandra, Pellenz, Felipe Mateus, Camargo, Joiza Lins, Moresco, Karla Suzana, Silva, Lucas Lima da, Aubin, Mariana Rauback, Oliveira, Mayara Souza de, Rech, Tatiana Helena, Canani, Luis Henrique Santos, Gerchman, Fernando, Leitão, Cristiane Bauermann, Crispim, Daisy
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/265579
• topic: SARS-CoV-2; COVID-19; Polimorfismo genético; Fatores de risco; Prognóstico; Genes; Mortalidade; Unidades de terapia intensiva; Cuidados críticos; Genótipo; Mortalidade; Polymorphisms; ACE1; IFIH1; IFNAR2; TMPRSS2; TYK2

Although advanced age, male sex, and some comorbidities impact the clinical course of COVID-19, these factors only partially explain the inter-individual variability in disease severity. Some studies have shown that genetic polymorphisms contribute to COVID-19 severity; however, the results are inconclusive. Thus, we investigated the association between polymorphisms in ACE1, ACE2, DPP9, IFIH1, IFNAR2, IFNL4, TLR3, TMPRSS2, and TYK2 and the clinical course of COVID-19. A total of 694 patients with COVID-19 were categorized as: (1) ward inpatients (moderate symptoms) or patients admitted at the intensive care unit (ICU; severe symptoms); and (2) survivors or non-survivors. In females, the rs1990760/IFIH1 T/T genotype was associated with risk of ICU admission and death. Moreover, the rs1799752/ACE1 Ins and rs12329760/TMPRSS2 T alleles were associated with risk of ICU admission. In non-white patients, the rs2236757/IFNAR2 A/A genotype was associated with risk of ICU admission, while the rs1799752/ACE1 Ins/Ins genotype, rs2236757/IFNAR2 A/A genotype, and rs12329760/TMPRSS2 T allele were associated with risk of death. Moreover, some of the analyzed polymorphisms interact in the risk of worse COVID19 outcomes. In conclusion, this study shows an association of rs1799752/ACE1, rs1990760/IFIH1, rs2236757/IFNAR2, rs12329760/TMPRSS2, and rs2304256/TYK2 polymorphisms with worse COVID19 outcomes, especially among female and non-white patients.