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

Maria Jiménez-Sousa,Salvador Resino,Esther Gómez-Sánchez,Alicia Gómez-Sanz,Eduardo Tamayo,Pilar Liu,Isidoro Martínez,Amanda Fernández-Rodríguez,Alejandra Fadrique,María Heredia-Rodríguez,Mario Lorenzo-López,Estefanía Gómez-Pesquera

doi:10.3390/jcm8030283

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.

Highlights

Sepsis is a life-threatening organ dysfunction that results from a dysregulated host response to infection [1]
We aimed to evaluate whether single nucleotide polymorphisms (SNPs) in several NF-κB-signaling-pathway-related genes are associated with susceptibility to infection, septic shock, and septic-shock-related death in European patients who underwent major abdominal or cardiac surgery
Significant differences are shown in bold. aOR adjusted odds ratio; 95% CI, 95% confidence interval; SNPs, single nucleotide polymorphisms; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TNFAIP3-interacting protein 1 (TNIP1), tumor necrosis factor alpha-induced protein 3 (TNFAIP3) (TNF alpha-induced protein 3) interacting protein 1

Summary

Introduction

Sepsis is a life-threatening organ dysfunction that results from a dysregulated host response to infection [1]. Septic shock is the most severe stage of sepsis and causes a substantial increase in mortality due to severe cellular and metabolic abnormalities [1]. 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. 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. The MyD88 rs7744 GG genotype was associated with a higher risk of death during 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

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