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. 2022 Dec 22;14(1):29.
doi: 10.3390/genes14010029.

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

Cristine Dieter  1   2 , Leticia de Almeida Brondani  1   3 , Natália Emerim Lemos  1 , Ariell Freires Schaeffer  2 , Caroline Zanotto  1 , Denise Taurino Ramos  1 , Eliandra Girardi  1 , Felipe Mateus Pellenz  1   2 , Joiza Lins Camargo  2   3   4 , Karla Suzana Moresco  5 , Lucas Lima da Silva  1 , Mariana Rauback Aubin  1 , Mayara Souza de Oliveira  1   2 , Tatiana Helena Rech  2   4 , Luís Henrique Canani  1   2   4 , Fernando Gerchman  1   2   4 , Cristiane Bauermann Leitão  1   2   4 , Daisy Crispim  1   2   4
Affiliations

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

Cristine Dieter et al. Genes (Basel). .

Abstract

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.

Keywords: ACE1; COVID-19; IFIH1; IFNAR2; SARS-CoV-2; TMPRSS2; TYK2; polymorphisms.

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Conflict of interest statement

The authors declare no conflict of interest.

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