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Published on: July 26, 2017
Association Between Single-Nucleotide Polymorphisms in Toll-like Receptor 3 (tlr3), tlr7, tlr8 and tirap Genes with
Adriana Souza Andrade1, Aline Almeida Bentes2,3, Lilian Martins Diniz2,3
1Instituto René Rachou/Fiocruz Minas, Belo Horizonte 30190-009, MG, Brazil.
Insights
Genetic variations in innate immune response genes, specifically TLR8, TLR7, TLR3, and TIRAP, are linked to severe COVID-19 outcomes in children. This finding helps understand why some pediatric cases become critical.
Area of Science:
- Genetics and Immunology
- Pediatric Infectious Diseases
- COVID-19 Pathogenesis
Background:
- COVID-19 has caused significant mortality globally, including in children, with respiratory symptoms and severe complications like SARS and MIS-C.
- Host genetic factors, particularly polymorphisms in immune response genes, are implicated in influencing COVID-19 severity.
- Understanding genetic predispositions in children is crucial for predicting disease progression and outcomes.
Purpose of the Study:
- To investigate the association between single-nucleotide polymorphisms (SNPs) in innate immune response genes and the severity of COVID-19 in hospitalized children.
- To identify specific genetic markers that may predict severe disease progression in pediatric SARS-CoV-2 infections.
Main Methods:
- Genotyping of 73 pediatric COVID-19 patients (under 13 years) using PCR and sequencing to analyze SNPs in TLR8, TLR7, TLR3, TIRAP, and MCP-1.
- Categorization of patients based on COVID-19 severity: mild, moderate, severe, and critical.
- Comparison of SNP frequencies against large population databases (Global ALFA, 1000 Genomes, gnomAD) and analysis of relative risk between severity groups.
Main Results:
- SNP frequencies in TLR8 (rs3764879), TLR7 (rs179008), TLR3 (rs3775291), and TIRAP (rs8177374) showed a higher relative risk associated with severe and critical COVID-19 compared to mild/moderate cases (p < 0.05).
- No significant association was found for SNPs in TLR8 (rs2407992) and MCP-1 (rs1024611).
- The SNP in TLR7 showed discrepant frequencies compared to global and American population databases.
Conclusions:
- Specific SNPs in innate immune response genes (TLR8, TLR7, TLR3, TIRAP) are associated with increased severity of COVID-19 in children.
- These genetic variations may play a role in the differential susceptibility to severe outcomes in pediatric SARS-CoV-2 infection.
- Further research into these genetic associations can inform risk stratification and potential therapeutic strategies for severe pediatric COVID-19.
Abstract:
The global number of COVID-19 deaths has reached 7 million, with 4% of these deaths occurring in children and adolescents. In Brazil, around 1500 children up to 11 years old died from the disease. The most common symptoms in children are respiratory, potentially progressing to severe illnesses, such as severe acute respiratory syndrome (SARS) and MIS-C. Studies indicate that comorbidities and genetic factors, such as polymorphisms in immune response genes, can influence the severity of COVID-19. This study investigates the occurrence of single-nucleotide polymorphisms (SNPs) in innate immune response genes in children with COVID-19. Seventy-three samples were analyzed from children under 13 years old hospitalized at João Paulo II Children's Hospital due to COVID-19. The evaluated SNPs were tlr8 (1) (rs3764879), tlr8 (2) (rs2407992), tlr7 (rs179008), tlr3 (rs3775291), tirap (rs8177374), and mcp-1 (rs1024611), considering four categories of severity: mild, moderate, severe, and critical COVID-19. To identify the SNPs, PCR and sequencing were performed. The frequencies of the SNPs obtained were not discrepant when compared to the frequencies described in the Global ALFA, Global 1000 Genomes, Global gnomAD, American 1000 Genomes, and American gnomAD databases, except for the SNP in TLR7. Comparing severe and critical cases to mild and moderate cases, we found a higher relative risk associated with mutations in tlr8 (1), tlr7, tlr3, and tirap (p < 0.05). No association was found for SNPs in tlr8 (2) and mcp-1. Our analyses suggest an association between SNPs in innate immune response genes and severity of symptoms in children with COVID-19 (or SARS-CoV-2 infected children).
