TLR4/NF-κB signaling pathway gene single nucleotide polymorphisms alter gene expression levels and affect ARDS occurrence and prognosis outcomes

Background: To study the occurrence and prognosis of acute respiratory distress syndrome (ARDS) using single nucleotide polymorphisms (SNPs) of TNF-alpha rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci in the TLR4/NF-kappa B pathway. Methods: Genotypes were analyzed for TNF-alpha rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci. Plasma TNF-alpha and IL-6 levels and MyD88 mRNA expression in peripheral blood mononuclear cells (PBMCs) of 300 ARDS patients and 300 non-ARDS patients (control group) were examined. The patients were followed up for 60 days, and the prognosis outcome was recorded. Results: The TNF-alpha rs1800629 locus A allele and the IL-6 rs1800796 locus Gallele were found to be risk factors for ARDS (adjusted OR=1.452, 95% CI: 1.211-1.689, P<.001 and adjusted OR=1.205, 95% CI: 1.058-1.358, P=.005, respectively). The G allele at MyD88 rs7744 locus was a protective factor against ARDS (adjusted OR=0.748, 95% CI: 0.631-0.876, P<.001). Compared with the other groups, homozygotes for TNF-alpha rs1800629, IL-6 rs1800796, and MyD88 rs7744 loci had higher expression levels, of which homozygotes for TNF-alpha rs1800629 and IL-6 rs1800796 loci had lower 60-day survival rates, while MyD88 rs7744 locus homozygotes had a higher 60-day survival rate. Conclusion: The effect of TNF-alpha rs1800629, IL-6 rs1800796, and MyD88 rs7744 SNPs on gene expression level is a likely cause of ARDS occurrence and poor prognosis.