ArticleCritical care (London, England)2011
Variants in the Toll-interacting protein gene are associated with susceptibility to sepsis in the Chinese Han population.
Article in Critical care (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Host genetic variants in sepsis risk: a field synopsis and meta-analysis.Critical care (London, England) · 2019Pooled it
- Review
- Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases.Autophagy · 2022Article
- Genetic association of TOLLIP gene polymorphisms and HIV infection: a case-control study.BMC infectious diseases · 2021Article
- Is there an Inflammation Role for MYD88 in Rheumatoid Arthritis?Inflammation · 2021Article
- Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets.International immunopharmacology · 2020Review
- Pathogenic Single Nucleotide Polymorphisms on Autophagy-Related Genes.International journal of molecular sciences · 2020Review
- Article
- Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia.Immunogenetics · 2018Article
- Toll-Interacting Protein, Tollip, Inhibits IL-13-Mediated Pulmonary Eosinophilic Inflammation in Mice.Journal of innate immunity · 2018Article
- Programming and memory dynamics of innate leukocytes during tissue homeostasis and inflammation.Journal of leukocyte biology · 2017Review
- Tollip SNP rs5743899 modulates human airway epithelial responses to rhinovirus infection.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2016Article
- MyD 88 Polymorphisms in Children Diagnosed with Sepsis.Balkan medical journal · 2016Article
- The influence of genetic polymorphisms in TLR4 and TIRAP, and their expression levels in peripheral blood, on susceptibility to sepsis.Experimental and therapeutic medicine · 2016Article
- Alteration of lysosome fusion and low-grade inflammation mediated by super-low-dose endotoxin.The Journal of biological chemistry · 2015Article
- Genetic variation in the tissue factor gene is associated with clinical outcome in severe sepsis patients.Critical care (London, England) · 2014Article
- The functional polymorphisms of miR-146a are associated with susceptibility to severe sepsis in the Chinese population.Mediators of inflammation · 2014Article
- Differential response to bacteria, and TOLLIP expression, in the human respiratory tract.BMJ open respiratory research · 2014Article
- Toll-like receptor-associated sequence variants and prostate cancer risk among men of African descent.Genes and immunity · 2013Article
- Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study.The Lancet. Respiratory medicine · 2013Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionDeregulated or excessive host immune responses contribute to the pathogenesis of sepsis. Toll-like receptor (TLR) signaling pathways and their negative regulators play a pivotal role in the modulation of host immune responses and the development of sepsis. The objective of this study was to investigate the association of variants in the TLR signaling pathway genes and their negative regulator genes with susceptibility to sepsis in the Chinese Han population.
methodsPatients with severe sepsis (n = 378) and healthy control subjects (n = 390) were enrolled. Five genes, namely TLR2, TLR4, TLR9, MyD88 and TOLLIP, were investigated for their association with sepsis susceptibility by a tag single nucleotide polymorphism (SNP) strategy. Twelve tag SNPs were selected based on the data of Chinese Han in Beijing from the HapMap project and genotyped by direct sequencing. The mRNA expression levels of TOLLIP were determined using real-time quantitative Polymerase Chain Reaction (PCR) assays, and concentrations of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).
resultsOur results showed that the minor C-allele of rs5743867 in TOLLIP was significantly associated with the decreased risk of sepsis (Padj = 0.00062, odds ratio (OR)adj = 0.71, 95% confidence interval (CI) 0.59 to 0.86) after adjustment for covariates in multiple logistic regression analysis. A 3-SNP haplotype block harboring the associated SNP rs5743867 also displayed strong association with omnibus test P value of 0.00049. Haplotype GTC showed a protective role against sepsis (Padj = 0.0012), while haplotype GCT showed an increased risk for sepsis (Padj = 0.00092). After exposure to lipopolysaccharide (LPS), TOLLIP mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from homozygotes for the rs5743867C allele were significantly higher than in heterozygotes and homozygotes for the rs5743867T allele (P = 0.013 and P = 0.01, respectively). Moreover, the concentrations of TNF-α and IL-6 in culture supernatants were significantly lower in the subjects of rs5743867CC genotype than in CT and TT genotype subjects (P = 0.016 and P = 0.003 for TNF-α; P = 0.01 and P = 0.002 for IL-6, respectively).
conclusionsOur findings indicated that the variants in TOLLIP were significantly associated with sepsis susceptibility in the Chinese Han population.
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