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

J Gene Med. 2021 Apr;23(4):e3323. doi: 10.1002/jgm.3323. Epub 2021 Feb 26.

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.

Keywords: endothelial nitric oxide synthase; polymorphism; sepsis; susceptibility; tumor necrosis factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Female
  • Gene Frequency
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type III / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Sepsis / blood
  • Sepsis / genetics*
  • Sepsis / pathology
  • Tumor Necrosis Factor-alpha / genetics*
  • Young Adult

Substances

  • Tumor Necrosis Factor-alpha
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III