CD14 C-159T and toll-like receptor 4 Asp299Gly polymorphisms in surviving meningococcal disease patients
Ariane Biebl1, Axel Muendlein, Zhyrgal Kazakbaeva
1Department of Pediatrics, University Teaching Hospital, Feldkirch, Austria. ariane.biebl@gespag.at
Background:
Carriage of Neisseria meningitidis occurs approximately in 10% of the population, onset of invasive meningococcal disease (IMD) cannot be predicted and differs between ages. It remains unclear, which host factors determine invasion of the bloodstream by the bacteria. Innate immunity has a very important role in the first recognition of invading pathogens. The functional single nucleotide polymorphisms (SNPs) CD14 C-159T and toll-like receptor 4 (TLR4) Asp299Gly have been associated with the risk of gram-negative infections. However, their role in development of IMD still remains unclear. Our aim was to investigate the influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of IMD.
Methodology/Principal Findings:
It was a retrospective case control study. Surviving Austrian meningococcal disease patients were enrolled by sending buccal swabs for DNA analysis. 185 cases with a proven meningococcal infection and 770 healthy controls were enrolled. In surviving meningococcal disease patients DNA analysis of CD14 C-159T and TLR 4 Asp299Gly polymorphisms was performed, as they are part of the innate immune response to bacterial determinants. CD14 C-159T and TLR4 Asp299Gly SNPs were not significantly associated with the presence of IMD when compared to healthy controls. The odds ratio for CD14 C-159T SNP was 1.14 (95% confidence interval (CI) 0.91-1.43; p = 0.266). In TLR4 Asp 299 Gly SNP the odds ratio was 0.78 (CI 0.47-1.43; p = 0.359).
Conclusion/Significance:
We could not observe a significant influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of developing IMD in surviving meningococcal disease patients. To our knowledge, this is the first study investigating the influence of the CD14 C-159T SNP on the susceptibility to IMD.
Insights
Genetic variations in CD14 and TLR4 do not significantly impact invasive meningococcal disease (IMD) risk. This study found no association between CD14 C-159T and TLR4 Asp299Gly polymorphisms and IMD susceptibility in surviving patients.
Area of Science:
- Immunogenetics
- Infectious Diseases
- Molecular Epidemiology
Background:
- Neisseria meningitidis carriage affects about 10% of the population, with unpredictable invasive meningococcal disease (IMD) onset.
- Host factors influencing bacterial bloodstream invasion and subsequent IMD remain largely unknown.
- Innate immunity plays a crucial role in pathogen recognition, with specific single nucleotide polymorphisms (SNPs) in CD14 and TLR4 implicated in gram-negative infections.
Purpose of the Study:
- To investigate the association between CD14 C-159T and TLR4 Asp299Gly polymorphisms and the risk of developing IMD.
- To determine if these innate immune gene variants influence susceptibility to invasive meningococcal disease.
Main Methods:
- A retrospective case-control study involving 185 surviving Austrian patients with confirmed meningococcal infection and 770 healthy controls.
- DNA analysis of buccal swabs was performed to genotype the CD14 C-159T and TLR4 Asp299Gly single nucleotide polymorphisms (SNPs).
- Statistical analysis compared the frequencies of these SNPs between IMD patients and controls to assess their association with disease risk.
Main Results:
- No significant association was found between the CD14 C-159T polymorphism and the presence of IMD (Odds Ratio = 1.14, p = 0.266).
- The TLR4 Asp299Gly polymorphism also showed no significant association with IMD risk (Odds Ratio = 0.78, p = 0.359).
- These findings indicate that the studied SNPs in CD14 and TLR4 do not appear to influence susceptibility to invasive meningococcal disease in the studied population.
Conclusions:
- The study did not find a significant influence of CD14 C-159T and TLR4 Asp299Gly polymorphisms on the risk of developing IMD.
- This is the first study, to our knowledge, to examine the impact of the CD14 C-159T SNP on susceptibility to invasive meningococcal disease.
- Further research may be needed to identify other host genetic factors contributing to IMD pathogenesis.
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