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

Abstract

Background Sepsis is a life‐threatening condition caused by a dysregulated host response to infections and is a leading cause of death in hospitalized patients. The present study aimed to elucidate the possible association between sepsis and the tumor necrosis factor (TNF) gene –308G/A (rs1800629) polymorphism, as well as endothelial nitric oxide synthase (eNOS, NOS3) gene –786T/C (rs2070744), 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Methods In total, 188 septic adult cases and 188 healthy controls were enrolled. Genomic DNAs from the controls and patients were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. Results There were significant associations between the G/G genotype and G allele of the TNF –308G/A (rs1800629) polymorphism in the sepsis group (p < 0.001). The presence of the T/C genotype (p = 0.002) and C allele (p = 0.001) of the –786T/C (rs2070744) was markedly associated with an increased risk of sepsis. However, no significant associations were found with 4a/4b (27 bp‐VNTR in intron 4, rs61722009) and 894G/T (Glu298Asp, rs1799983) polymorphisms. Higher 4bGC and lower 4bTT haplotype frequencies were associated with sepsis. Conclusions Our results strongly suggest that TNF gene (−308G/A, rs1800629) and NOS3 gene –786T/C (rs2070744) polymorphisms may modify individual susceptibility to sepsis in the Turkish population.

Intrinsic endothelial hyperresponsiveness to inflammatory mediators drives acute episodes in models of Clarkson disease

“…That the functional endothelial defect persists after passaging further suggests that the susceptibility of ISCLS-derived ECs to cytokine hypersensitivity is durable and raises the possibility of a genetic abnormality underlying the stress-induced endothelial phenotype. Although related studies of more common conditions have proposed that genetically determined variance in the host vascular response may contribute to the risk for other leakage pathologies (e.g., sepsis) ( 43 – 45 ), to our knowledge, there is no known hyperpermeability disorder in which the vasculature is genetically (or epigenetically) programmed to “hyperrespond” to otherwise routine stimuli.…”

CIAP1/2 can regulate the inflammatory response and lung injury induced by apoptosis in septic rats

“…25,26 However, sepsis leads to excessive cytokine release, causing an imbalance in microvascular endothelial barrier permeability, worsening microvascular leakage, and ultimately leading to circulatory failure and multi-organ dysfunction. 27,28 The TNF receptor (TNFR)-mediated activation of the NF-kB and MAPK pathways induces an inflammatory response that exacerbates the sepsis inflammatory response, [29][30][31][32] However, TNFR also mediates cell apoptosis, which helps to mitigate the inflammatory response. 5,6 Thus, the regulation of the two opposing factions in the TNF pathway is an important topic worth further exploration.…”