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Functional Single-Nucleotide Polymorphisms in the MBL2 and TLR3 Genes Influence Disease Severity in Influenza A

Manohar Lal Choudhary1, Urmila Chaudhary1, Malvika Salve1

  • 1ICMR-National Institute of Virology, Pune, India.

Viral Immunology
|February 23, 2022
PubMed

Insights

Host genetics influence influenza A (H1N1)pdm09 severity. Specific single-nucleotide polymorphisms (SNPs) in Toll-like receptor 3 (TLR3) and Mannose-binding lectin 2 (MBL2) genes were associated with severe outcomes in infected individuals.

Area of Science:

  • Immunogenetics
  • Virology
  • Human Genetics

Background:

  • Host genetic factors significantly impact the clinical outcome of influenza A (H1N1)pdm09 virus infections.
  • Understanding these genetic determinants is crucial for predicting disease severity and developing targeted interventions.

Purpose of the Study:

  • To investigate the association between single-nucleotide polymorphisms (SNPs) in key immune-related genes and the severity of influenza A (H1N1)pdm09 virus infection.
  • To identify specific genetic markers that correlate with severe disease manifestations.

Main Methods:

  • A case-control study was conducted with 86 severe and 293 mild influenza A (H1N1)pdm09 virus-infected cases from western India.
  • Genotyping of SNPs in IFITM, MBL2, TLR3, TLR8, DDX58, IFIH1, CD55, and FCGR2 genes was performed using PCR-based methods.

Main Results:

  • A significantly higher frequency of the TLR3 rs5743313 T/T genotype and the TLR3 two-locus haplotype rs3775291-rs3775290 T-A was observed in severe cases.
  • Conversely, a lower frequency of the MBL2 rs1800450 mutant allele and the TLR3 rs3775291-rs3775290 T-G haplotype was noted in severe cases compared to mild cases.
  • No significant differences in allele and genotype frequencies were found for other investigated SNPs between the groups.

Conclusions:

  • Functional single-nucleotide polymorphisms (SNPs) in the MBL2 and TLR3 genes are associated with severe disease outcomes in individuals infected with the influenza A (H1N1)pdm09 virus.
  • These findings highlight the role of specific genetic variations in modulating the host's response to influenza infection.
Keywords:
IFITM3MBL2TLR3TNFAgene polymorphismsinfluenza A (H1N1)pdm09 virus

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