Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis

Abstract

Background:The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha.Aims:To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels.Study Design:Case-control study.Methods:Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction–restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay.Results:We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05).Conclusion:Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

The interplay between inflammatory pathways and COVID-19: A critical review on pathogenesis and therapeutic options

“…NFκ light chain enhancer of B cells (NFκB) is another mechanism associated with cytokine storm. NF-κB dimers are encoded by NF-κB genes and regulate transcription of several crucial proteins of inflammation including TNFα [ 37 ]. Since TNF-α induces signaling transduction through NFκB, TNFα-NF-κB inflammatory signaling pathway can also be considered as a potential target of COVID-19 [ 38 ].…”

Ticagrelor Can Be an Important Agent in the Treatment of Severe COVID-19 Patients with Myocardial Infarction

“…In cases of pneumonia developing due to coronavirus disease 2019 (COVID-19), it has been shown that 71.4% of non-survivors and 0.6% of survivors had disseminated intravascular coagulation (DIC), and the majority of non-survivors had increased D-dimer level (1). TNF-α and IL-6 variants are also known to be risk factors for pneumonia-induced septic shock in intensive care patients (2). We believe that the ADP receptor inhibitor, ticagrelor, should be considered in the treatment of concomitant COVID-19 pneumonia and myocardial infarction (MI) because it may contribute to patient survival.…”

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

“…In sepsis patients, TNF gene polymorphisms have been described in various populations. Some investigators have identified the association between the TNF –308G/A (rs1800629) polymorphism and elevated susceptibility to severe sepsis, 12,13,16,29–31 whereas others failed to confirm this 32–36 . Song et al 29 .…”