TNFAIP3, TNIP1, and MyD88 Polymorphisms Predict Septic-Shock-Related Death in Patients Who Underwent Major Surgery

Abstract

Background: In many immune-related diseases, inflammatory responses and several clinical outcomes are related to increased NF-κB activity. We aimed to evaluate whether SNPs related to the NF-κB signaling pathway are associated with higher susceptibility to infection, septic shock, and septic-shock-related death in European patients who underwent major surgery. Methods: We performed a case-control study on 184 patients with septic shock and 212 with systemic inflammatory response syndrome, and a longitudinal substudy on septic shock patients. Thirty-three SNPs within genes belonging to or regulating the NF-κB signaling pathway were genotyped by Agena Bioscience’s MassARRAY platform. Results: No significant results were found for susceptibility to infection and septic shock in the multivariate analysis after adjusting for multiple comparisons. Regarding septic-shock-related death, patients with TNFAIP3 rs6920220 AA, TNIP1 rs73272842 AA, TNIP1 rs3792783 GG, and TNIP1 rs7708392 CC genotypes had the highest risk of septic-shock-related death in the first 28 and 90 days. Also, the MyD88 rs7744 GG genotype was associated with a higher risk of death during the first 90 days. Haplotype analysis shows us that patients with the TNIP1 GAG haplotype (composed of rs73272842, rs3792783, and rs7708392) had a lower risk of death in the first 28 days and the TNIP1 AGC haplotype was associated with a higher risk of death in the first 90 days. Conclusions: The SNPs in the genes TNFAIP3, TNIP1, and MyD88 were linked to the risk of septic-shock-related death in patients who underwent major surgery.

Extensive Changes in Transcriptomic “Fingerprints” and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused by Neisseria meningitidis

“…Several inhibitors/modulators of the proinflammatory response such as NFKB1A-, TNFAIP3-, TNFAIP6-, TNIP1-, and IRAK3 mRNA ( Figure 7A and Additional File 3: Table S1) were found to be regulated in lungs of the studied patients, suggesting modulation of the macrophages in the lungs from pro-to an anti-inflammatory phenotype. These molecules are associated with poor outcome (Pino-Yanes et al, 2011;Mittal et al, 2016;Jimenez-Sousa et al, 2019).…”

OLFM4 polymorphisms predict septic shock survival after major surgery

“…We also used other SNPs ( TNFAIP3 rs6920220; and TNIP1 rs73272842, rs3792783 and rs7708392) related to NF‐kB signalling pathway, which were recently reported in our cohort, 30 to adjust multivariate regression models. The selection of these SNPs was made based on the fact that OLFM4 expression is regulated by the NF‐kB signalling pathway 19 and their previous associations with mortality in septic shock patients 30 …”