ArticleBMC medical genetics2010
Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury.
Article in BMC medical genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 31 citations in OpenAlex.
- The Novel Role of the Expression of Toll-like Receptors TLR-5, TLR-6, and TLR-9 and Associated Up-Regulation of Programmed Cell Death 1 Receptor (PD-1) and Its Ligand (PD-L1) in Lung Sepsis.International journal of molecular sciences · 2025Article
- Association Between Single-Nucleotide Polymorphisms inViruses · 2024Article
- Article
- Sesamin attenuates intestinal injury in sepsis via the HMGB1/TLR4/IL-33 signalling pathway.Pharmaceutical biology · 2020Article
- Association of variants in selected genes mediating host immune response with duration of Staphylococcus aureus bacteremia.Genes and immunity · 2020Article
- Influence of single nucleotide polymorphisms (SNPs) in genetic susceptibility towards periprosthetic osteolysis.Genes & genomics · 2019Review
- Article
- 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
- Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility.Immunologic research · 2015Review
- GADD45a promoter regulation by a functional genetic variant associated with acute lung injury.PloS one · 2014Article
- Assessing the quality of studies supporting genetic susceptibility and outcomes of ARDS.Frontiers in genetics · 2014Article
- Non-essential role for TLR2 and its signaling adaptor Mal/TIRAP in preserving normal lung architecture in mice.PloS one · 2013Article
- Genetic variation in the TNF receptor-associated factor 6 gene is associated with susceptibility to sepsis-induced acute lung injury.Journal of translational medicine · 2012Article
- Integrative assessment of chlorine-induced acute lung injury in mice.American journal of respiratory cell and molecular biology · 2012Article
- Genetic variation in Toll-like receptors and disease susceptibility.Nature immunology · 2012Review
- Association of genetic variants in the IRAK-4 gene with susceptibility to severe sepsis.World journal of emergency medicine · 2012Article
- Structural insights into TIR domain specificity of the bridging adaptor Mal in TLR4 signaling.PloS one · 2012Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundToll like receptors (TLRs) signaling pathways, including the adaptor protein Mal encoded by the TIRAP gene, play a central role in the development of acute lung injury (ALI). Recently, the TIRAP variants have been described association with susceptibility to inflammatory diseases. The aim of this study was to investigate whether genetic variants in TIRAP are associated with the development of ALI.
methodsA case-control collection from Han Chinese of 298 healthy subjects, 278 sepsis-associated ALI and 288 sepsis alone patients were included. Three tag single nucleotide polymorphisms (SNPs) of the TIRAP gene and two additional SNPs that have previously showed association with susceptibility to other inflammatory diseases were genotyped by direct sequencing. The differences of allele, genotype and haplotype frequencies were evaluated between three groups.
resultsThe minor allele frequencies of both rs595209 and rs8177375 were significantly increased in ALI patients compared with both healthy subjects (odds ratio (OR) = 1.47, 95% confidence interval (CI):1.15-1.88, P = 0.0027 and OR = 1.97, 95% CI: (1.38-2.80), P = 0.0001, respectively) and sepsis alone patients (OR = 1.44, 95% CI: 1.12-1.85, P = 0.0041 and OR = 1.82, 95% CI: 1.28-2.57, P = 0.00079, respectively). Haplotype consisting of these two associated SNPs strengthened the association with ALI susceptibility. The frequency of haplotype AG (rs595209A, rs8177375G) in the ALI samples was significantly higher than that in the healthy control group (OR = 2.13, 95% CI: 1.46-3.09, P = 0.00006) and the sepsis alone group (OR = 2.24, 95% CI: 1.52-3.29, P = 0.00003). Carriers of the haplotype CA (rs595209C, rs8177375A) had a lower risk for ALI compared with healthy control group (OR = 0.69, 95% CI: 0.54-0.88, P = 0.0003) and sepsis alone group (OR = 0.71, 95% CI: 0.55-0.91, P = 0.0006). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons.
conclusionsThese results indicated that genetic variants in the TIRAP gene might be associated with susceptibility to sepsis-associated ALI in Han Chinese population. However, the association needs to be replicated in independent studies.
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