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.