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Polymorphisms in ACE1, TMPRSS2, IFIH1, IFNAR2, and TYK2 Genes Are Associated with Worse Clinical Outcomes in COVID-19

2022; Multidisciplinary Digital Publishing Institute; Volume: 14; Issue: 1 Linguagem: Inglês

10.3390/genes14010029

ISSN

2073-4425

Autores

Cristine Dieter, Letícia de Almeida Brondani, Natália Emerim Lemos, Ariell F. Schaeffer, Caroline Zanotto, Denise Taurino Ramos, Eliandra Girardi, Felipe Mateus Pellenz, Joíza Lins Camargo, Karla Suzana Moresco, Lucas Lima da Silva, Mariana Rauback Aubin, Mayara Souza de Oliveira, Tatiana Helena Rech, Luís Henrique Santos Canani, Fernando Gerchman, Cristiane Bauermann Leitão, Daisy Crispim,

Tópico(s)

Immune responses and vaccinations

Resumo

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 COVID-19 outcomes. In conclusion, this study shows an association of rs1799752/ACE1, rs1990760/IFIH1, rs2236757/IFNAR2, rs12329760/TMPRSS2, and rs2304256/TYK2 polymorphisms with worse COVID-19 outcomes, especially among female and non-white patients.

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