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Assessing the Impact of TLR4 rs4986790 Polymorphism on Bacterial Meningitis Risk: A Systematic Review and

Praveen Kumar Chandra Sekar1, Ramakrishnan Veerabathiran

  • 1Human Cytogenetics and Genomics Laboratory, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, India.

Annals of Indian Academy of Neurology
|November 22, 2024
PubMed
Abstract

Insights

This meta-analysis reveals a strong link between Toll-like receptor 4 (TLR4) rs4986790 polymorphism and susceptibility to meningococcal and pneumococcal meningitis. These findings highlight TLR4

Area of Science:

  • Immunogenetics
  • Infectious Diseases
  • Molecular Epidemiology

Background:

  • Toll-like receptor 4 (TLR4) gene is implicated in the pathogenesis of bacterial meningitis.
  • Previous studies on the association between TLR4 rs4986790 polymorphism and bacterial meningitis susceptibility yielded inconsistent results.
  • Meningococcal and pneumococcal meningitis are significant public health concerns.

Purpose of the Study:

  • To conduct a meta-analysis evaluating the association between TLR4 rs4986790 polymorphism and susceptibility to meningococcal meningitis.
  • To assess the association between TLR4 rs4986790 polymorphism and susceptibility to pneumococcal meningitis.
  • To resolve inconsistencies in previous research regarding TLR4 polymorphism and bacterial meningitis risk.

Main Methods:

  • Comprehensive literature search of PubMed, Embase, and Google Scholar databases up to May 31, 2024.
  • Inclusion of 14 case-control studies comprising 3599 cases and 7438 controls.
  • Meta-analysis performed using random-effects and fixed-effects models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) under various genetic models (GG+GA vs. AA, GA vs. AA, GG vs. AA, G vs. A).

Main Results:

  • A significant correlation was observed between TLR4 polymorphisms and meningococcal meningitis across multiple genetic models (e.g., GG+GA vs. AA: OR=0.34, P=0.01).
  • A significant association was found for pneumococcal meningitis in the GG vs. AA model (OR=0.35, P=0.02).
  • The meta-analysis utilized Cochrane RoB 2 tool and Metagenyo for robust statistical analysis.

Conclusions:

  • The meta-analysis demonstrates a strong correlation between TLR4 rs4986790 polymorphism and susceptibility to both meningococcal and pneumococcal meningitis.
  • The findings suggest a potential role for TLR4 genetic variations in the risk of these bacterial meningitis types.
  • Further research involving diverse populations is recommended to validate and strengthen these results.

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