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Association between polymorphisms in TLR3, TICAM1 and IFNA1 genes and covid-19 severity in Southern Brazil
Matheus Braga1, Mariana Akemi Sonoda Shiga1, Pedro Emanuel Santiago Silva2
1Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, Paraná, Brazil.
Insights
Certain genetic variations in Toll-like receptor 3 (TLR3), TICAM1, and interferon alpha 1 (IFNA1) influence Coronavirus disease 2019 (Covid-19) severity. These single nucleotide polymorphisms (SNPs) offer protection or increase the risk of severe Covid-19 outcomes.
Area of Science:
- Immunogenetics
- Virology
- Genomics
Background:
- Severe Coronavirus disease 2019 (Covid-19) presents a distinct phenotype characterized by impaired type I interferon response and heightened inflammation.
- Understanding the genetic underpinnings of Covid-19 severity is crucial for predicting patient outcomes.
Purpose of the Study:
- To investigate the association between single nucleotide polymorphisms (SNPs) in immune response genes and Covid-19 severity.
- Examined SNPs in TLR3, TICAM1, IFNA1, TNF, and IL6.
Main Methods:
- A cross-sectional study involving 300 Covid-19 patients in Brazil (150 non-severe, 150 severe/critical).
- Genotyping was performed for specific SNPs in five immune-related genes.
Main Results:
- The T/T genotype of TLR3 (rs3775291) showed 58% protection against severe Covid-19.
- TICAM1 genotypes (rs2292151) offered 57-71% protection against severe Covid-19.
- IFNA1 genotype (rs1758566) variations were associated with an increased risk of critical Covid-19.
Conclusions:
- SNPs rs3775291 (TLR3), rs2292151 (TICAM1), and rs1758566 (IFNA1) can significantly influence Covid-19 severity.
- These genetic markers may play a role in modulating the host immune response to SARS-CoV-2 infection.
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.
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