Journal Article

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

Banescu, Claudia, Badea, Iudita, Moldovan, Valeriu, Dobreanu, Minodora, Chirtes, Ioana Raluca, Georgescu, Anca Meda, Hutanu, Adina, Azamfirei, Leonard, Voidazan, Septimiu, Azamfirei, Razvan

2020

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Adult / Aged / Aged, 80 and over / Alleles / Antigens / Biomarkers / Chronic illnesses / Chronic obstructive pulmonary disease / Critical Illness / Cytokines / Disease / Disease Progression / Disease Susceptibility / Evaluation / Female / Haplotypes / Haplotypes - genetics / Healthcare-associated infection control / Homozygosity / Homozygote / Hospital Mortality / Hospitals / Humans / Immunoglobulins / Infections / Infectious Diseases / Internal Medicine / Male / Medical Microbiology / Medicine / Medicine & Public Health / Middle Aged / Mortality / Nucleotides / Parasitology / Patients / Physiology / Polymorphism / Polymorphism, Single Nucleotide / Prognosis / Promoter Regions, Genetic / Prospective Studies / Research Article / Risk / Sepsis / Shock, Septic - genetics / Shock, Septic - mortality / Single nucleotide polymorphism / Software / Statistical analysis / Studies / TNF-α / Tropical Medicine / Tumor Necrosis Factor-alpha - genetics / Tumor necrosis factor-TNF / Tumor necrosis factor-α