Association of tumor necrosis factor-2 allele with plasma tumor necrosis factor-alpha levels and mortality from septic shock

Appoloni, Olivier; Dupont, Elisabeth; Vandercruys, Marleen; Andriens, M.; Duchateau, Jean; Vincent, Jean‐Louis

doi:10.1016/s0002-9343(01)00656-8

Cited by 65 publications

(41 citation statements)

References 13 publications

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“…In particular, we were unable to confirm previous findings of significant associations between the TNF À308 and the LTA þ 249 SNPs and susceptibility to, or outcome from severe sepsis and septic shock. 7-9,24-26 Also, in keeping with one earlier study, 7 we were unable to confirm previous findings of an association between either the TNF À308 SNP 8,25 or the LTA þ 249 SNP 9 and circulating levels of TNF. Such inconsistency has been a common experience with candidate gene association studies in many diseases, 35 and in particular with those which have examined TNF polymorphisms.…”

Section: Discussioncontrasting

confidence: 60%

“…Sample size and statistical analysis Power calculations were informed by previous TNF À308 studies 7,8,[23][24][25][26] with regard to estimating allele frequency and previous audits in the participating hospitals in order to estimate mortality rates. It was calculated that in a case-control study with a relative risk for mortality of 2.5 (overall ICU mortality of 30%) and a À308 A allele frequency of 0.2 (frequency of G/A and A/A 0.4) 200 patients would provide 480% power to detect a difference between the two groups with Po0.05 (two-sided P-value).…”

Section: Haplotype Analysismentioning

confidence: 99%

“…6 Since then, a number of relatively small studies have suggested that interindividual variations in susceptibility to, and outcome from, severe sepsis/septic shock can be partly explained by polymorphisms of the genes encoding proteins involved in mediating and controlling innate immunity and the inflammatory response. [7][8][9][10][11][12][13][14][15][16][17][18] Tumour necrosis factor (TNF) is a pivotal cytokine in the host response to infection. Systemic administration of TNF produces most of the symptoms and signs of sepsis, 19,20 and previous studies have shown that high TNF levels are associated with a poor outcome from meningococcal infection.…”

Section: Introductionmentioning

confidence: 99%

“…Although several studies have found an association of the A allele with a predisposition to septic shock and/or outcome from sepsis, findings have been inconsistent (Table 1). 7,8,[23][24][25][26] One explanation for these contradictory observations may be the linkage disequilibrium (LD), which is known to exist between this SNP and other functionally important polymorphisms in the region, and it is notable that only one previous study has investigated TNF haplotype associations in patients with sepsis. 26 Moreover, although the A allele of the À308 SNP has been shown to increase TNF transcription in some in vitro studies, 27 in others this has not been the case, 28 leading some to question the functional importance of this SNP.…”

Section: Introductionmentioning

confidence: 99%

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TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

et al. 2004

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Tumour necrosis factor (TNF) is an important pro-inflammatory cytokine produced in sepsis. Studies examining the association of individual TNF single nucleotide polymorphisms with sepsis have produced conflicting results. This study investigated whether common polymorphisms of the TNF locus and the two receptor genes, TNFRSF1A and TNFRSF1B, influence circulating levels of encoded proteins, and whether individual polymorphisms or extended haplotypes of these genes are associated with susceptibility, severity of illness or outcome in adult patients with severe sepsis or septic shock. A total of 213 Caucasian patients were recruited from eight intensive care units (ICU) in the UK and Australia. Plasma levels of TNF (P ¼ 0.02), sTNFRSF1A (P ¼ 0.005) and sTNFRSF1B (P ¼ 0.01) were significantly higher in those who died on ICU compared to those who survived. There was a positive correlation between increasing soluble receptor levels and organ dysfunction (increasing SOFA score) (sTNFRSF1A R ¼ 0.51, Po0.001; sTNFRSF1B R ¼ 0.53, Po0.001), and in particular with the degree of renal dysfunction. In this study, there were no significant associations between the selected candidate TNF or TNF receptor polymorphisms, or their haplotypes, and susceptibility to sepsis, illness severity or outcome. The influence of polymorphisms of the TNF locus on susceptibility to, and outcome from sepsis remains uncertain.

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Section: Discussioncontrasting

confidence: 60%

Section: Haplotype Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

et al. 2004

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“…For example, a polymorphism of the TNF-alpha gene, the TNF-2 allele, is associated with increased serum levels of TNF and a greater risk of mortality from septic shock. (19) Moreover, single nucleotide polymorphisms, microsatellites, insertion and deletion polymorphisms are all forms of genetic variation that can characterize an individual's risk for sepsis, organ dysfunction, or death. (20) Most genetic traits associated with severe infection are associated with defects in innate immune responses.…”

Section: Introductionmentioning

confidence: 99%

Entendendo o conceito PIRO: da teoria à prática clínica - Parte 1

Rabello¹,

Rosolem²,

Leal³

et al. 2009

Rev. bras. ter. intensiva

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Despite recent advances in diagnosis and care of critically ill patients sepsis related mortality rate remains unacceptably high. Therefore, new methods of evaluation are necessary to provide an earlier and more accurate characterization of septic patients. Based on the (oncologic) TNM system, the PIRO concept was introduced as a new staging system for sepsis in order to assess risk and predict prognosis, with potential to assist in inclusion of patients in clinical studies and estimate the probability of response of patients to specific therapeutic interventions.

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Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients

Özkan

Günay

Şener

et al. 2021

The Journal of Gene Medicine

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Background Sepsis is a life‐threatening condition caused by a dysregulated host response to infections and is a leading cause of death in hospitalized patients. The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene –308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene –786T/C (rs2070744), 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Methods In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. Results There were significant associations between the G/G genotype and G allele of the TNF –308G/A (rs1800629) polymorphism in the sepsis group (p < 0.001). The presence of the T/C genotype (p = 0.002) and C allele (p = 0.001) of the –786T/C (rs2070744) was markedly associated with an increased risk of sepsis. However, no significant associations were found with 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Higher 4bGC and lower 4bTT haplotype frequencies were associated with sepsis. Conclusions Our results strongly suggest that TNF gene (−308G/A, rs1800629) and NOS3 gene –786T/C (rs2070744) polymorphisms may modify individual susceptibility to sepsis in the Turkish population.

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Association of tumor necrosis factor-2 allele with plasma tumor necrosis factor-alpha levels and mortality from septic shock

Cited by 65 publications

References 13 publications

TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

Entendendo o conceito PIRO: da teoria à prática clínica - Parte 1

Variants in TNF and NOS3 (eNOS) genes associated with sepsis in adult patients

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