Polymorphisms of the toll-like receptor 2 and 4 genes are associated with faster progression and a more severe course of sepsis in critically ill patients

@article{Nachtigall2014PolymorphismsOT,
  title={Polymorphisms of the toll-like receptor 2 and 4 genes are associated with faster progression and a more severe course of sepsis in critically ill patients},
  author={Irit Nachtigall and Andrey Tamarkin and Sascha Tafelski and Andreas Weimann and Andreas Rothbart and Susanne Heim and Klaus Wernecke and Claudia D. Spies},
  journal={Journal of International Medical Research},
  year={2014},
  volume={42},
  pages={110 - 93}
}
Objective To determine whether the Arg753Gln polymorphism of the toll-like receptor 2 (TLR2) gene and the Asp299Gly polymorphism of the TLR4 gene in critically ill patients affect their clinical outcomes. Methods Medical and surgical patients in three intensive care units (ICU) were enrolled in this prospective study. TLR2 and TLR4 gene polymorphisms were determined using restriction fragment length polymorphism analysis. Results A total of 145 patients were included in this study: 28 patients… 
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No associations established between single nucleotide polymorphisms in human Toll‐like receptor 2 and Toll‐interacting protein and Staphylococcus aureus bloodstream infections

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The present meta-analysis supports a direct effect of the TLR2 Arg753Gln polymorphism on sepsis risk, especially in Europeans, and might be used as a relevant risk estimate for the development of sepsi.

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The data indicate that FcγRIIA genotyping can be used as a marker of genetic susceptibility to sepsis and that allele G, associated with the R131 genotype, was significantly more frequent in septic patients than in the other groups.

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References

SHOWING 1-10 OF 43 REFERENCES

Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections.

Findings indicate that hTLR4 mutations are associated with an increased incidence of gram-negative infections in critically ill patients in a surgical setting.

Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts

Carriers of mutations in sequential components of the TLR signaling system may have an increased risk for severe infections, and this genotype showed a decrease in cytokine release when infected which was not apparent in patients with sterile inflammation following cardiac surgery.

The presence of functionally relevant toll-like receptor polymorphisms does not significantly correlate with development or outcome of sepsis.

The genotype frequencies of functionally relevant SNPs in TLR2, 4 and 5 in critically ill patients from a multidisciplinary surgical intensive care unit (ICU) were determined and none of the investigated SNPs clearly predicted outcome of sepsis-related multiorgan failure.

Effects of functional Toll‐like receptor‐4 mutations on the immune response to human and experimental sepsis

The results suggest that the signalling capacity of TLR4 as affected by loss‐of‐function mutations does not influence human or experimental sepsis caused by polymicrobial infection, and other innate immune receptors may compensate forTLR4 defects.

High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR

This work has developed a rapid and inexpensive method for the detection of both single nucleotide polymorphisms based on restriction fragment length polymorphism and found that the ratio of heterozygous for the Arg753Gln polymorphism is significantly higher than previously reported.

Toll-like receptor 4 polymorphisms and atherogenesis.

The Asp299Gly TLR4 polymorphism, which attenuates receptor signaling and diminishes the inflammatory response to gram-negative pathogens, is associated with a decreased risk of atherosclerosis, consistent with the hypothesis that innate immunity may play a part in atherogenesis.

Modulation of tissue Toll-like receptor 2 and 4 during the early phases of polymicrobial sepsis correlates with mortality.

Early increases in TLR2/4 gene and TLR4 protein expression correlation with mortality, whereas blunting TLR gene and protein expression correlated with improved long-term survival suggests that early up-regulation of tissue TLR 2/4 may play a role in the proinflammatory response and pathophysiology of polymicrobial sepsis.

Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications.

Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock.

Patients with septic shock with the TLR4 Asp299Gly/Thr399Ile alleles had a higher prevalence of gram-negative infections and mutations in theTLR4 receptor may predispose people to develop septicshock with gram- negative microorganisms.

Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease.