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

ABSTRACT: BACKGROUND:The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-?) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-? 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-? 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-??+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-? promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-? levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-? levels in septic shock. CONCLUSIONS:TNF-??+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-? SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

SUBMITTER: Georgescu AM 

PROVIDER: S-EPMC7071754 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature