Genetic association study of tumor necrosis factor-alpha with sepsis and septic shock in Thai pediatric patients

Phumeetham, Suwannee; Chat-Uthai, Nunthawut; Manavathongchai, Manutham; Viprakasit, Vip

doi:10.2223/jped.2216

Cited by 14 publications

(16 citation statements)

References 28 publications

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“…Among them, 12 studies were conducted in Asian populations , 10 in Caucasian populations , and four in mixed populations (more than two ethnic groups) . A majority of studies (80.8%) were performed in adult populations, only four studies in pediatric populations . The type of sepsis included sepsis (n = 15), severe sepsis (n = 3), septic shock (n = 2), and mixed patient groups (n = 6).…”

Section: Resultsmentioning

confidence: 99%

“…In 2010, Teuffel et al performed a systematic review and meta‐analysis and found that TNF ‐α −308G/A polymorphism was associated with sepsis but not sepsis mortality . Since 6 years have passed and more evidence has been published , it is of great value to update the results. Moreover, the study conducted by Teuffel et al only focused on TNF‐α −308G/A polymorphism .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor necrosis factor-α −308G/A and −238G/A polymorphisms are associated with increased risks of sepsis: evidence from an updated meta-analysis

Zhang

Zhao

Liu

2017

APMIS

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Previous studies have reported the relationship between tumor necrosis factor-α (TNF-α) -308G/A and -238G/A polymorphisms and sepsis risk with inconsistent results. The aim of this study was to estimate the association of the two polymorphisms with risk of sepsis or sepsis-related mortality using a meta-analysis. PubMed, Embase, and Web of Science databases were searched up to June 20 2016. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed or random effect model. Twenty-six studies were included in this meta-analysis. Overall, an increased sepsis risk of TNF-α -308G/A was observed (GA vs GG: OR = 1.43, 95% CI: 1.07-1.92; GA/AA vs GG: OR = 1.42, 95% CI: 1.06-1.89). Subgroup analyses showed that the significant association was found in Asians (GA vs GG: OR = 1.63, 95% CI: 1.01-2.63) and adult patients. Similarly, an increased sepsis risk of TNF-α -238G/A was observed in overall and subgroup analyses. However, no significant association was found between TNF-α -308G/A and -238G/A polymorphisms and sepsis-related mortality. These findings indicate that both TNF-α -308G/A and -238G/A polymorphisms were associated with increased risks of sepsis but not sepsis-related mortality. Further studies with larger sample size are needed to confirm these results.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-α −308G/A and −238G/A polymorphisms are associated with increased risks of sepsis: evidence from an updated meta-analysis

Zhang

Zhao

Liu

2017

APMIS

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“…Low levels of TNF-α and IL-1β have been correlated with septic shock and increased risk of bacterial infections. [12][13][14][15] High levels of circulating IL-6 are commonly implicated in inflammatory diseases, tissue damage, uncontrolled activation of macrophage cells, and increased rate of infections. 12,13,16 These observations may provide insight to the fulminant action of Ab-acquired pneumonia in which the patient typically presents with bacteremia and septic shock leading to death.…”

Section: Cr3 Ismentioning

confidence: 99%

Alcohol impairs J774.16 macrophage-like cell antimicrobial functions inAcinetobacter baumanniiinfection

et al. 2013

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Acinetobacter baumannii (Ab) is a common cause of community-acquired pneumonia (caP) in chronic alcoholics in tropical and sub-tropical climates and associated with a >50% mortality rate. We demonstrated that exposure of J774.16 macrophage-like cells to physiological alcohol (etOh) concentrations decreased phagocytosis and killing of Ab. etOh-mediated macrophage phagocytosis dysfunction may be associated with reduced expression of GtPase-rhoa, a key regulator of the actin polymerization signaling cascade. etOh inhibited nitric oxide (NO) generation via inducible NO-synthase inactivation, which enhanced Ab survival within macrophages. additionally, etOh alters cytokine production resulting in a dysregulated immune response. this study is a proof of principle which establishes that etOh might exacerbate Ab infection and be an important factor enhancing caP in individuals at risk.

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“…TNF-α has been involved in sepsis immunodepression through increased apoptosis [18]. The significant contribution of the TNF-α to the pathology of the inflammatory response generated the idea of a possible genetic determinism of its circulating levels and hence of sepsis risk and evolution [12,13,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. The single nucleotide polymorphism (SNP) at position -308 in the promoter region of the TNF-α gene is the most studied in sepsis and has been associated with higher transcription rates of the cytokine and, more often than not, with an increased risk of sepsis [13,18,32,36,37].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

et al. 2020

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Background: The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. Methods: We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A,-238G/A,-376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. Results: TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34-0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21-0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. Conclusions: TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

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Genetic association study of tumor necrosis factor-alpha with sepsis and septic shock in Thai pediatric patients

Cited by 14 publications

References 28 publications

Tumor necrosis factor-α −308G/A and −238G/A polymorphisms are associated with increased risks of sepsis: evidence from an updated meta-analysis

Tumor necrosis factor-α −308G/A and −238G/A polymorphisms are associated with increased risks of sepsis: evidence from an updated meta-analysis

Alcohol impairs J774.16 macrophage-like cell antimicrobial functions inAcinetobacter baumanniiinfection

Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression

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