Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease?

Balding, Joanna; Healy, C. Mary; Livingstone, Wendy; White, Barry; Mynett-Johnson, Lesley; Cafferkey, Mary T.; Smith, Owen

doi:10.1038/sj.gene.6364020

Cited by 72 publications

(70 citation statements)

References 57 publications

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“…In this situation, the clinical outcome depends to a great extent on the patients' genetics. Many studies have demonstrated the importance of underlying genetics in modulating the sepsis phenotype [7,[17][18][19][20][21], and Sorensen et al established the inheritance pattern of those predisposed to mortality due to infectious disease [37]. This is one of the reasons we decided to evaluate certain polymorphisms in this study.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, many publications focused their attention on using the plasma levels of certain factors, such as protein C (PC), procalcitonin, TNF-, and plasminogen activator inhibitor-1 (PAI-1), as prognostic markers [14][15][16]. Other publications have investigated specific genetic polymorphisms in candidate genes [7,10,[17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

“…Specific genetic factors might predict the risk not only for developing severe infection, but also for developing organ dysfunction leading to death [18][19][20]. Among TNF-α variants, a polymorphism that affects TNF-α expression has been located at nucleotide position -308 (TNF-α rs1800629 G/A) and has been associated with morbidity and mortality in severe forms of fulminant purpura, mucocutaneous leishmaniasis and sepsis [28].…”

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%

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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“…Balding et al 126 associated IL1RA variable number of tandem repeats SNPs with susceptibility to MD (including one-third meningitis cases), but studies by Carrol et al 127 and a meta-analysis of Brouwer et al…”

Section: Snps In Cytokine Genesmentioning

confidence: 99%

“…Severity and mortality of MD was associated with IL6-174 G/G and IL10-1082 A/A, but not with LTA þ 252, TNF-308, IL10-592, or IL1b SNPs. 126 Significant associations of cytokine genes with susceptibility to meningococcal infections are summarized in Table 1.…”

mentioning

confidence: 99%

Genetic variation of innate immune response genes in invasive pneumococcal and meningococcal disease applied to the pathogenesis of meningitis

et al. 2011

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Interleukin-10 ?1082 G/A polymorphism and risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

et al. 2005

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IL-10 is an anti-inflammatory cytokine that may have a protective role in acute lung injury. IL-10 expression is affected by a single-nucleotide polymorphism (SNP) located at position -1082 (G to A). The A allele is associated with lower IL-10 production. Low IL-10 production has been linked to the development of BPD. Thus, the IL-10 -1082 SNP may be a genetic risk factor for the development of BPD in the premature newborn. The IL-10 -1082 SNP was determined in 294 (235 African American, 56 Caucasian, and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants and compared to outcome (death and/or development of BPD). Differences in groups were analyzed using ANOVA (continuous variables) or chi square (proportions). The frequency of the A allele in our population was 0.62. Thirty-nine (13.3%) infants were homozygous GG, 146 (49.7%) were heterozygous GA, and 109 (37.0%) were homozygous AA. There were no significant differences between genotype groups with respect to ethnic origin, gender, need for surfactant replacement therapy, and isolation of Ureaplasma urealyticum or Mycoplasma hominis from tracheal aspirates at birth. However, AA infants were slightly more mature and of greater birth weight than GA infants (26.9 +/- 0.2 weeks vs. 26.3 +/- 0.2 weeks, P < 0.05, and 940 +/- 22 g vs. 882 +/- 18 g, P < 0.05, respectively). There was no significant effect of the IL-10 -1082 SNP on mortality or the development of BPD (O2 on 28 days or 36 weeks postconceptional age). However, when considered together, the IL-10 -1082 AA/GA genotypes (lower IL-10 production) were associated with a trend toward reduction in risk for the combined outcome of BPD or death (18/39 vs. 80/255, respectively; P = 0.068). The incidence of other complications of prematurity (retinopathy of prematurity, intraventricular hemorrhage, or periventricular leukomalacia) was not different between groups. In conclusion, the IL-10 -1082 G/A SNP does not have a major influence on mortality or the development of BPD in ventilated VLBW infants.

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Genomic polymorphic profiles in an Irish population with meningococcaemia: is it possible to predict severity and outcome of disease?

Cited by 72 publications

References 57 publications

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

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

Genetic variation of innate immune response genes in invasive pneumococcal and meningococcal disease applied to the pathogenesis of meningitis

Interleukin-10 ?1082 G/A polymorphism and risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

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