ArticlePloS one2010
TLR4 Asp299Gly and Thr399Ile polymorphisms: no impact on human immune responsiveness to LPS or respiratory syncytial virus.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Association between Toll-Like Receptor 4 Polymorphisms and Systemic Lupus Erythematosus Susceptibility: A Meta-Analysis.BioMed research international · 2016Pooled it
- ERVK activity in CD8Journal of neuroinflammation · 2026Article
- Molecular Analysis of miR-155 and MIR155HG Mutations in Conjunction with TLR4 Variants in Inflammatory Joint Disease.Current issues in molecular biology · 2026Article
- Scratching the Surface Takes a Toll: Immune Recognition of Viral Proteins by Surface Toll-like Receptors.Viruses · 2022Review
- Impact of genetic polymorphisms related to innate immune response on respiratory syncytial virus infection in children.Virus genes · 2022Review
- A mouse model of human TLR4 D299G/T399I SNPs reveals mechanisms of altered LPS and pathogen responses.The Journal of experimental medicine · 2021Article
- Article
- Expression of Human Endogenous Retrovirus-K in Spinal and Bulbar Muscular Atrophy.Frontiers in neurology · 2019Article
- Toll-Interleukin 1 Receptor Domain-Containing Adaptor Protein 180L Single-Nucleotide Polymorphism Is Associated With Susceptibility to Recurrent Pneumococcal Lower Respiratory Tract Infections in Children.Frontiers in immunology · 2018Article
- House Dust Endotoxin Levels Are Associated with Adult Asthma in a U.S. Farming Population.Annals of the American Thoracic Society · 2017Article
- The innate immune response to RSV: Advances in our understanding of critical viral and host factors.Vaccine · 2017Review
- Comparison of the Expression Changes after Botulinum Toxin Type A and Minocycline Administration in Lipopolysaccharide-Stimulated Rat Microglial and Astroglial Cultures.Frontiers in cellular and infection microbiology · 2017Article
- Expression level of human TLR4 rather than sequence is the key determinant of LPS responsiveness.PloS one · 2017Article
- Association of Single Nucleotide Polymorphisms in Toll-like Receptor Genes With Asthma Risk: A Systematic Review and Meta-analysis.Allergy, asthma & immunology research · 2015Article
- Functional polymorphisms in toll-like receptor 4 are associated with worse outcome in acute ischemic stroke patients.Neuroreport · 2014Article
- Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis.World journal of gastroenterology · 2013Article
- Respiratory syncytial virus--a comprehensive review.Clinical reviews in allergy & immunology · 2013Review
- Host-Viral Interactions: Role of Pattern Recognition Receptors (PRRs) in Human Pneumovirus Infections.Pathogens (Basel, Switzerland) · 2013Article
- Coding variants of TLR2 and TLR4 genes do not substantially contribute to prosthetic joint infection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2013Article
- Genetics and genomics in pediatric septic shock.Critical care medicine · 2012Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundA broad variety of natural environmental stimuli, genotypic influences and timing all contribute to expression of protective versus maladaptive immune responses and the resulting clinical outcomes in humans. The role of commonly co-segregating Toll-like receptor 4 (TLR4) non-synonymous single nucleotide polymorphisms Asp299Gly and Thr399Ile in this process remains highly controversial. Moreover, what differential impact these polymorphisms might have in at risk populations with respiratory dysfunction, such as current asthma or a history of infantile bronchiolitis, has never been examined. Here we determine the importance of these polymorphisms in modulating LPS and respiratory syncytial virus (RSV)--driven cytokine responses. We focus on both healthy children and those with clinically relevant respiratory dysfunction. METHODOLOGY: To elucidate the impact of TLR4 Asp299Gly and Thr399Ile on cytokine production, we assessed multiple immune parameters in over 200 pediatric subjects aged 7-9. Genotyping was followed by quantification of pro- and anti-inflammatory cytokine responses by fresh peripheral blood mononuclear cells upon acute exposure to LPS or RSV. PRINCIPAL
findingsIn contrast to early reports, neither SNP influenced immune responses evoked by LPS exposure or RSV infection, as measured by the intermediate phenotype of pro- and anti-inflammatory cytokine responses to these ubiquitous agents. There is no evidence of altered sensitivity in populations with "at risk" clinical phenotypes. CONCLUSIONS/SIGNIFICANCE: Genomic medicine seeks to inform clinical practice. Determination of the TLR4 Asp299Gly/Thr399Ile haplotype is of no clinical benefit in predicting the nature or intensity of cytokine production in children whether currently healthy or among specific at-risk groups characterized by prior infantile broncholitis or current asthma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.