The common functional C(−159)T polymorphism within the promoter region of the lipopolysaccharide receptor CD14 is not associated with sepsis development or mortality

Hubacek, Jaroslav A.; Stüber, Frank; Fröhlich, D.; Book, Malte; Wetegrove, Silke; Rothe, Gregor; Schmitz, Gerd

doi:10.1038/sj.gene.6363691

Cited by 62 publications

(27 citation statements)

References 24 publications

(33 reference statements)

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“…19 Carriage of the T allele of CD14À159 has also been associated with an increased mortality rate from septic shock, 14 although other groups could not confirm this finding. 15 Here we found that cells from individuals with the CD14À159TT genotype produced higher levels of TNFa mRNA after exposure to LPS, E. coli and S. pneumoniae.…”

Section: Discussionmentioning

confidence: 59%

“…14 However a similar study in a German cohort found no such association. 15 We hypothesised that the impact of the LTA+250 and CD14À159 polymorphisms on TNFa production may depend on whether the individual is exposed to Gram-positive or Gram-negative bacteria. As previous in vivo and in vitro studies have only assessed cytokine levels in serum or culture supernatants, we assessed TNFa mRNA and intracellular protein concentrations.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFα production induced by Gram-positive and Gram-negative bacteria

et al. 2003

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Improved understanding of how host genetic variation affects resistance to microbial pathogens could lead to better treatment and/or prevention of infectious diseases. The lymphotoxin alpha (LTA)+250 and CD14À159 polymorphisms are associated with differences in susceptibility or outcome to several infections. We stimulated peripheral blood mononuclear cells (PBMC) from 22 healthy individuals with purified lipopolysaccharide (LPS), heat-killed Escherichia coli or Streptococcus pneumoniae. TNFaintracellular protein levels were measured by flow cytometry and mRNA was quantitated by RT-PCR. TNFa mRNA levels were higher in LTA+250GG subjects after 4 h incubation with LPS compared with LTA+250AA (T test, P ¼ 0.001). In contrast, after 8 h incubation with S. pneumoniae, there was slightly more TNFa mRNA in cells from LTA+250AA subjects. After 4 h incubation with LPS or E. coli, CD14À159TT subjects had higher TNFa mRNA levels than CD14À159CC (P ¼ 0.05, 0.033, respectively). Neither polymorphism affected the proportion of cells expressing intracellular TNFa protein. This suggests that the polymorphisms affected transcription and that other regulatory mechanisms affect production of TNFa protein. The effect of these two polymorphisms on TNFa mRNA production is stimulus dependent, with opposite effects observed for Gram-positive and Gram-negative stimuli.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFα production induced by Gram-positive and Gram-negative bacteria

et al. 2003

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“…26,27 Findings have also been conflicting in patients with severe sepsis, with some studies observing no association and another finding a relationship between the T-allele and death from sepsis. 17,28,29 TNF-α has been demonstrated to play a major role in the pathogenesis of sepsis and its complications after burn injury. [30][31][32][33] Furthermore, there is evidence that a guanine to adenine substitution (G→A) at nucleotide -308 within the TNF-α promoter affects transcriptional regulation.…”

Section: Discussionmentioning

confidence: 99%

Innate Immunity SNPs are Associated with Risk for Severe Sepsis after Burn Injury

Barber

Chang

Arnoldo

et al. 2006

Clinical Medicine & Research

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“…(d)two hundred and forty seven healthy subjects (119 females and 128 males), genotyped already in a previous study [42] , served as controls. Patients and controls were Caucasians and their geographical origin was southern Germany.…”

Section: Patients and Controlsmentioning

confidence: 99%

Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection

Meiler

Mühlbauer²,

Johann³

et al. 2005

WJG

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Abstract Abstract AbstractAIM: Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD) and chronic hepatitis C virus (HCV) infection. METHODS:CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls. Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined. RESULTS:The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci, serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However, no association was found between CD14 genotypes and histological staging or grading. CONCLUSION:Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.

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The common functional C(−159)T polymorphism within the promoter region of the lipopolysaccharide receptor CD14 is not associated with sepsis development or mortality

Cited by 62 publications

References 24 publications

Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFα production induced by Gram-positive and Gram-negative bacteria

Polymorphisms in lymphotoxin alpha and CD14 genes influence TNFα production induced by Gram-positive and Gram-negative bacteria

Innate Immunity SNPs are Associated with Risk for Severe Sepsis after Burn Injury

Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection

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