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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

I. Nachtigall, A. Tamarkin, S. Tafelski, A. Weimann, A. Rothbart, S. Heim, K. Wernecke, C. Spies
Published 2014 · Medicine

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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 carried heterozygous mutations (10 in the TLR2 gene, 19 in the TLR4 gene, and one combined) and 117 patients were wild type. Severe sepsis was observed in 33% of wild types (n = 38), 60% of the TLR2 group (n = 6), and 63% of the TLR4 group (n = 12); the difference was significant between the TLR4 and wild type groups. Both TLR groups demonstrated a shorter time-to-onset of severe sepsis or septic shock. Only the TLR4 group demonstrated significant progression towards septic shock compared with the wild type group. Length of ICU stay was significantly prolonged in the TLR4 group compared with the wild type group, but not in the TLR2 group. Conclusions Two common SNPs of the TLR2 and TLR4 genes – Arg753Gln and Asp299Gly – were associated with a shorter time-to-onset of severe sepsis or septic shock in patients admitted to the ICU.
This paper references
10.1038/76048
TLR4 mutations are associated with endotoxin hyporesponsiveness in humans
N. Arbour (2000)
10.1016/j.metabol.2010.01.005
Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications.
S. Devaraj (2011)
Toll-like receptor-2 mediates lipopolysaccharideinduced cellular signalling
RB Yang (1998)
CDC definitions for nosocomial infections, 1988.
(1989)
10.1128/CDLI.11.6.1194-1197.2004
Lack of Association between Toll-Like Receptor 2 Polymorphisms and Susceptibility to Severe Disease Caused by Staphylococcus aureus
C. Moore (2004)
10.1016/S1473-3099(05)01308-3
Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease.
N. Schröder (2005)
10.1007/s00109-003-0443-x
High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR
N. Schröder (2003)
10.1152/ajplung.00025.2008
Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium.
J. Koff (2008)
10.1001/ARCHINTE.162.9.1028
Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock.
E. Lorenz (2002)
10.1046/j.1365-2567.2003.01674.x
Effects of functional Toll‐like receptor‐4 mutations on the immune response to human and experimental sepsis
C. Feterowski (2003)
10.1128/IAI.73.4.2075-2082.2005
Differential Involvement of Toll-Like Receptors 2 and 4 in the Host Response to Acute Respiratory Infections with Wild-Type and Mutant Haemophilus influenzae Strains
E. Lorenz (2005)
10.1097/CCM.0b013e318192fbaf
Toll-like receptor pathway signaling is differently regulated in neutrophils and peripheral mononuclear cells of patients with sepsis, severe sepsis, and septic shock*
R. Salomão (2009)
10.1203/PDR.0b013e3181559774
Monocyte mRNA Phenotype and Adverse Outcomes From Pediatric Multiple Organ Dysfunction Syndrome
M. Hall (2007)
10.1007/s00134-007-0934-2
Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
R. P. Dellinger (2007)
10.1016/S1074-7613(00)80119-3
Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components.
O. Takeuchi (1999)
10.1038/26239
Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling
R. Yang (1998)
10.4049/jimmunol.165.10.5392
Cutting Edge: TLR2-Deficient and MyD88-Deficient Mice Are Highly Susceptible to Staphylococcus aureus Infection1
O. Takeuchi (2000)
10.1172/JCI31008
TLR4 activation mediates kidney ischemia/reperfusion injury.
H. Wu (2007)
10.1038/labinvest.2010.158
TLR2 expression and signaling-dependent inflammation impair wound healing in diabetic mice
M. Dasu (2010)
10.1016/j.cell.2006.03.047
Phosphoinositide-Mediated Adaptor Recruitment Controls Toll-like Receptor Signaling
J. Kagan (2006)
10.1089/gtmb.2010.0258
The presence of functionally relevant toll-like receptor polymorphisms does not significantly correlate with development or outcome of sepsis.
P. Ahmad-Nejad (2011)
10.1165/RCMB.2003-0388OC
Activation of airway epithelial cells by toll-like receptor agonists.
Q. Sha (2004)
10.1073/PNAS.250476497
The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors.
A. Ozinsky (2000)
10.1001/jama.1993.03510240069035
A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.
J. Le Gall (1993)
10.1097/CCM.0b013e31827e83af
Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock 2012
R. Dellinger (2013)
Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients
中田 孝明 (2006)
10.1155/2010/568396
Toll-like Receptor 4 Modulation as a Strategy to Treat Sepsis
X. Wittebole (2010)
10.1016/0196-6553(88)90053-3
CDC definitions for nosocomial infections, 1988.
J. Garner (1988)
10.1097/00003246-198608000-00027
APACHE II--a severity of disease classification system.
J. Legall (1986)
10.1073/PNAS.0601527103
Toll-like receptor 4 plays a crucial role in the immune-adrenal response to systemic inflammatory response syndrome.
K. Zacharowski (2006)
10.1186/CC2193
The PIRO concept: P is for predisposition
D. Angus (2003)
10.1007/s00134-008-1040-9
Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008
R. Dellinger (2008)
10.1161/01.CIR.0000112575.66565.84
Reduced Myocardial Ischemia-Reperfusion Injury in Toll-Like Receptor 4-Deficient Mice
J. Oyama (2004)
Use of the SOFA score to assess the incidence of organ dysfunction/failure in 108 Journal of International Medical Research 42(1) intensive care units: results of a multicenter, prospective study
JL Vincent (1998)
10.1097/01.CCM.0000069343.27691.F3
Modulation of tissue Toll-like receptor 2 and 4 during the early phases of polymicrobial sepsis correlates with mortality.
D. Williams (2003)
10.1038/gene.2008.100
A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma
M. Bjørnvold (2009)
10.1086/344893
Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections.
D. Agnese (2002)
10.1097/00003246-199811000-00016
Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine.
J. Vincent (1998)
10.1128/IAI.72.3.1828-1831.2004
Heterozygous Toll-Like Receptor 2 Polymorphism Does Not Affect Lipoteichoic Acid-Induced Chemokine and Inflammatory Responses
S. von Aulock (2004)
10.1056/NEJMOA012673
Toll-like receptor 4 polymorphisms and atherogenesis.
S. Kiechl (2002)
10.1152/AJPREGU.00412.2003
Hemorrhage-induced acute lung injury is TLR-4 dependent.
K. Barsness (2004)
10.1097/00003246-199601000-00012
Simplified Therapeutic Intervention Scoring System: the TISS-28 items--results from a multicenter study.
D. Miranda (1996)
10.1186/cc9047
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
O. Kumpf (2010)



This paper is referenced by
10.1055/s-0040-1714710
Role of Toll-Like Receptors 2 and 4 Genes Polymorphisms in Neonatal Sepsis in a Developing Country: A Pilot Study
Bedewy M. Khaled (2020)
10.1177/0300060517719768
Mortality, intensive care treatment, and cost evaluation: Role of a polymerase chain reaction assay in patients with sepsis.
A. Markota (2018)
10.1177/0300060517719768
Mortality, intensive care treatment, and cost evaluation: Role of a polymerase chain reaction assay in patients with sepsis
M. Andrej (2017)
Pathogenic variants in TIRAP and MyD88 are not associated withneonatal sepsis in a South Indian population.
D BenetBoscoDhas (2014)
10.1089/gtmb.2014.0004
Gene polymorphisms and febrile neutropenia in acute leukemia--no association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 are associated with the disease in Turkish patients: a preliminary study.
M. Pehlivan (2014)
10.1038/srep38947
The relationship between toll like receptor 4 gene rs4986790 and rs4986791 polymorphisms and sepsis susceptibility: A meta-analysis
R. Liu (2016)
10.1038/gene.2014.67
Polymorphisms of Toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in acute myeloid leukemia
U. Schnetzke (2014)
10.1111/apm.12734
No associations established between single nucleotide polymorphisms in human Toll‐like receptor 2 and Toll‐interacting protein and Staphylococcus aureus bloodstream infections
Tom Eirik Smeland (2017)
10.1177/1753425915605892
Gene expression analysis in human polymorphonuclear leukocytes stimulated by LPSs from nosocomial opportunistic pathogens
T. Ubagai (2015)
10.1007/s00280-018-3729-y
Toll-like receptor/interleukin-1 domain innate immune signalling pathway genetic variants are candidate predictors for severe gastrointestinal toxicity risk following 5-fluorouracil-based chemotherapy
Samantha K Korver (2018)
10.1002/jbt.22503
Correlation between TICAM1 gene polymorphisms and community-acquired pneumonia in children.
Y. Yang (2020)
10.1016/j.bbmt.2015.05.011
Donor Nucleotide-Binding Oligomerization-Containing Protein 2 (NOD2) Single Nucleotide Polymorphism 13 Is Associated with Septic Shock after Allogeneic Stem Cell Transplantation.
M. Grube (2015)
10.1007/s10753-015-0275-1
Fc Gamma Receptor IIA (CD32A) R131 Polymorphism as a Marker of Genetic Susceptibility to Sepsis
Jaqueline Beppler (2015)
10.1097/SPC.0000000000000202
Toll-like receptors in the pathogenesis of chemotherapy-induced gastrointestinal toxicity
E. Cario (2016)
10.1002/ijc.30734
Gram‐positive pneumonia augments non‐small cell lung cancer metastasis via host toll‐like receptor 2 activation
Stephen D Gowing (2017)
10.25560/47969
Mathematical modelling of epithelium homeostasis
Elisa Domínguez Hüttinger (2014)
10.1038/ncomms12304
Toll-like receptor 2 activation depends on lipopeptide shedding by bacterial surfactants
Dennis Hanzelmann (2016)
10.1016/j.imbio.2014.10.006
Genetic polymorphisms of innate and adaptive immunity as predictors of outcome in critically ill patients.
M. Kompoti (2015)
10.1016/j.jtho.2019.07.023
Gram-Negative Pneumonia Augments Non-Small Cell Lung Cancer Metastasis Through Host Toll-like Receptor 4 Activation.
Stephen D Gowing (2019)
10.7554/eLife.18496
RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate immunity
Alison C. McKelvey (2016)
Interleukin-6 enhances glucagon secretion: Amplification via the pancreas and brain
Tammy M Barnes (2015)
63-68 Dr Vishnu- Benet
Benet Bosco Dhas (2014)
10.1186/s13054-015-1130-3
Association between the TLR2 Arg753Gln polymorphism and the risk of sepsis: a meta-analysis
Jun-wei Gao (2015)
10.4236/IJOHNS.2014.34034
The Anterior Spreader Flap: A Minimally Invasive Alternative to the Auto Spreader Flap in the Treatment of Patients with Nasal Valve Dysfunction
S. Bessler (2014)
10.1016/j.jcrc.2018.05.012
Toll‐like receptor 2, 4 and 9 polymorphisms and their association with ICU‐acquired infections in Central Greece
M. Chatzi (2018)
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