Association between polymorphisms in TLR3, TICAM1 and IFNA1 genes and covid-19 severity in Southern Brazil

Expert Rev Mol Diagn. 2024 Jun;24(6):525-531. doi: 10.1080/14737159.2024.2367466. Epub 2024 Jun 17.

Abstract

Background: A distinct phenotype in Coronavirus disease 2019 (Covid-19) was observed in severe patients, consisting of a highly impaired interferon (IFN) type I response, an exacerbated inflammatory response.

Objective: The aim of the present study was to investigate a possible association of single nucleotide polymorphisms (SNPs), in five genes related to the immune response, rs3775291 in TLR3; rs2292151 in TICAM1; rs1758566 in IFNA1; rs1800629 in TNF, and rs1800795 in IL6 with the severity of Covid-19.

Methods: A cross-sectional study was performed, with non-severe and severe/critical patients diagnosed with Covid-19, by two public hospitals in Brazil. In total, 300 patients were genotyped for the SNPs, 150 with the non-severe form of the disease and 150 with severe/critical form.

Results: The T/T genotype of TLR3 in recessive model shows 58% of protection against severe/critical Covid-19; as well as the genotypes G/A+A/A of TICAM1 in dominant model with 60% of protection, and in a codominant model G/A with 57% and A/A with 71% of protection against severe/critical Covid-19. Comparing severe and critical cases, the T/C genotype of IFNA1 in the codominant model and TC+C/C in the dominant model showed twice the risk of critical Covid-19.

Conclusion: We can conclude that rs3775291, rs2292151 and rs1758566 can influence the COVID-19 severity.

Keywords: Toll like receptor; coronavirus; cytokines; innate immune response; polymorphism.

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Adult
  • Aged
  • Brazil / epidemiology
  • COVID-19* / genetics
  • COVID-19* / virology
  • Cross-Sectional Studies
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Interferon Type I / genetics
  • Interferon-alpha
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • SARS-CoV-2* / genetics
  • Severity of Illness Index*
  • Toll-Like Receptor 3* / genetics

Substances

  • Interferon Type I
  • Interferon-alpha
  • Toll-Like Receptor 3
  • IFNA1 protein, human
  • TLR3 protein, human
  • TICAM1 protein, human
  • Adaptor Proteins, Vesicular Transport