Abstract

OBJECTIVE: The study aimed to investigate the role of TNFα-308 genetic polymorphism, association between TNF-α serum level and prognostic factor of mortality in pediatric sepsis. 
 
 METHODS: This was a prospective cohort study. Consecutive sampling method was used and samples were obtained from septic patients diagnosed based on the IPSC 2005 criteria. Serum TNF-α and genetic polymorphism were measuread and analyzed with ELISA and PCR plus sequencing, respectively.
 
 RESULT: One hundred and seventeen samples were included, 62 were in survivor grioup and 55 in non survivor group. A very significant association was found between TNF-α serum level and mortality (p<0.001). The optimal cut off point of TNFα serum level as prognostic factor for mortality was ≥ 500 pg/mL (p<0.001 and OR 16.6) sensitivity 78.1%, specificity 82%, Positive Predictive Value (PPV) 79.6%, Negative Predictive Value (NPV) 80.9%, Area Under Curve (AUC) 0.811. Two samples showed TNFα-308A polymorphism and mutation of GG allele to heterozygote GA allele. Neither TNFα polymorphism and TNFα serum level showed any association with mortality. There was no significant association between TNFα-308 polymorphism and TNF-α serum level p=0.461(p>0.05) and mortality p=0.219 (p>0.05), all sample who had TNFα-308 genetic polymorphism were in non survivor group and had TNF-α serum level ≥ 500 pg/mL. 
 
 CONCLUSION: Genetic polymorphism of TNF-α-308 showed no statistic significant on mortality, but all subjects with TNFα-308 polymorphism had higher TNF-α serum and were all in non-survivor group.

Highlights

  • Sepsis, which is usually caused by infection can lead to severe systemic inflammation

  • The optimal cut off point of TNFα serum level as prognostic factor for mortality was ≥ 500 pg/mL (p

  • There was no significant association between TNFα-308 polymorphism and TNF-α serum level p=0.461(p>0.05) and mortality p=0.219 (p>0.05), all sample who had TNFα-308 genetic polymorphism were in non survivor group and had TNF-α serum level ≥ 500 pg/mL

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Summary

Methods

Consecutive sampling method was used and samples were obtained from septic patients diagnosed based on the IPSC 2005 criteria. Serum TNF-α and genetic polymorphism were measuread and analyzed with ELISA and PCR plus sequencing, respectively

Result
Introduction
Patients and Controls
Cytokine Serum Consentration
Analysis of Gene Polymorpism TNF-α -308
Sequencing
Statistics Analysis
Results
Characteristics of the Subjects
Mortality Cutt off Point of TNF-α in Sepsis Patients
Association between TNFα-308 Genetic Polymorphism and TNF-α Serum Level
Association between TNFα- 308 Genetic Polymorphism and Sepsis Outcome
Discussion
Full Text
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