4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia

Geishofer, Gotho; Binder, A.; Müller, Martin; Zöhrer, Bettina; Resch, Bernhard; Müller, Wilhelm; Faber, Jörg; Finn, Adam; Endler, Georg; Mannhalter, Christine; Zenz, Werner

doi:10.1007/s00431-005-1673-4

Cited by 68 publications

(38 citation statements)

References 33 publications

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“…The study of the association between the most common polymorphism, PAI-1 rs1799889 4G/5G, and the resolution of the septic process has been a predictable focus of interest [29][30][31][32]. In fact, our group has previously published an article reporting that the presence of the PAI-1 4G allele was a good predictor of a fatal outcome [38].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the PAI-1 gene contains a polymorphism (PAI-1 rs1799889 4G/5G, either 4 or 5 guanine bases) in which the PAI-1 4G allele produces more PAI-1 than the PAI-1 5G allele during an acute phase response, such as in sepsis. In fact, the PAI-1 rs1799889 4G/5G polymorphism has been found to correlate with a poor outcome in meningococcal sepsis [29][30][31][32]. Specific polymorphisms in the encoding of this gene have been suggested to correlate an increased mortality in septic shock, although contradictory results have been presented [33].…”

Section: Introductionmentioning

confidence: 99%

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Biomarkers in sepsis at time zero: intensive care unit scores, plasma measurements and polymorphisms in Argentina

Wingeyer

Cunto

Nogueras

et al. 2011

J Infect Dev Ctries

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Introduction: A patient's response to sepsis is influenced by their genetic background. Our objective was to use plasma markers, such as protein C (PC), D-dimer, Plasminogen Activator Inhibitor-1 (PAI-1) levels, and the PAI-1 rs1799889 4G/5G and Tumor Necrosis Factor-α rs1800629 G/A polymorphisms to improve classical intensive care unit (ICU) scores. Methodology: We studied 380 subjects, 166 with sepsis. We performed coagulation tests: plasma PAI-1 and PC levels were evaluated by chromogenic methods; and D-dimer was evaluated by immunoturbidimetric assay. Polymorphisms were performed using for polymerase chain reactions followed by digest with specific restriction enzyme. We acquired the APACHE and SOFA scores (time zero), sex, age, body mass index, associated co-morbidities, length of ICU stay (days), the severity of sepsis (sepsis, severe sepsis or septic shock), the HIV status and the ICU outcome (survival or death). Results: We found significant differences between patients who died (n=80) and those who survived (n=86) in terms of the ICU length of stay (6 vs. 10 days), septic shock (64 versus 24%), age (51 versus 38 years old), HIV+ condition (34 versus 16%), SOFA (7 versus 4), APACHE (19 versus 13), D-dimer (4.32 versus 2.88 g/ml), PC (46.0 versus 63.5 %) and PAI-1 (33.0 versus 16.5 UA/l). When we used a regression analysis with dichotomized variables, only the SOFA 4 , PAI-1 16 , HIV status and the PAI-1 4G allele proved to be predictors of death at time zero. Conclusions: In the future, ICU scores may be further improved by adding certain genomic or plasma data.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biomarkers in sepsis at time zero: intensive care unit scores, plasma measurements and polymorphisms in Argentina

Wingeyer

Cunto

Nogueras

et al. 2011

J Infect Dev Ctries

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“…Individuals homozygous for the 4G allele produce more PAI-1 than either individuals heterozygous (4G/5G) or homozygous for the 5G allele [268]. In children with meningococcal disease, those with the 4G/4G genotype had higher plasma levels of PAI-1 [269] and a higher mortality compared with children with either the 4G/5G or 5G/5G genotypes [269][270][271]. Other adult and pediatric studies also demonstrate a higher mortality in those individuals homozygous for the 4G allele genotype in a variety of infectious diseases [272][273][274].…”

Section: Plasminogen Activator Inhibitor-1(pai-1)mentioning

confidence: 99%

Host Genetics and Pediatric Sepsis

Quasney¹

2011

TOINFJ

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Susceptibility to, and outcome from, sepsis in children is highly variable due in part to genetic variation in genes coding for components of the innate immune response. This review article will discuss evidence for the influence of host genetic variability on the susceptibility to, and outcome from, sepsis in children and adults. Polymorphisms in genes coding for proteins involved in the recognition of bacterial pathogens (TLR4, CD-14, Fc RIIa, and mannose binding lectin) and the response to bacterial pathogens (TNF-, IL-1 , IL-1 , IL-1 RA , IL-6, IL-10, heat shock proteins, ACE, plasminogen activator inhibitor-1) can influence the amount or function of the protein produced in response to bacterial stimuli. Evidence is discussed suggesting that some of these genetic polymorphisms influence the susceptibility to, and outcome from, sepsis. Conclusion:Host genetic variability in the regulatory and coding regions of genes for components of the innate immune system may influence the susceptibility to and/or outcome from sepsis. The disparate results observed in many studies of polymorphisms in sepsis emphasize the need for future studies to be larger, to include the analysis of multiple polymorphisms, and to be better designed with respect to control populations in order to identify the degree of influence that genetic variability has on sepsis.

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“…Furthermore, SNPs have also been found in genes expressing proteins participating into the inflammatory response. These genes, which SNPs may show correlation with septic shock are: Lymphotoxin Alpha (LTA) (Gu et al 2007, Temple et al 2004, Yuan et al 2003, Ye et al 1995, Binder et al 2007, Geishofer et al 2005, Haralambous et al 2003, Hermans et al 1999, Van der Poll et al 2001, Hubacek et al 2001, Waterer et al 2001. As discussed in this chapter there are many biomarkers of sepsis.…”

Section: Genetic Biomarkers-single Nucleotide Polymorphismsmentioning

confidence: 99%