Dataset Information

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

ABSTRACT: 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. 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. 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. 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.

SUBMITTER: Jimenez-Sousa MA

PROVIDER: S-EPMC6463255 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Jiménez-Sousa Maria Ángeles MÁ Fadrique Alejandra A Liu Pilar P Fernández-Rodríguez Amanda A Lorenzo-López Mario M Gómez-Sánchez Esther E Gómez-Sanz Alicia A Heredia-Rodríguez María M Gómez-Pesquera Estefanía E Martínez Isidoro I Tamayo Eduardo E Resino Salvador S

Journal of clinical medicine 20190226 3

<h4>Background</h4>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.<h4>Methods</h4>We performed a case-control study on 184 patients with septic shock and 212 with systemic inflammatory response syn ...[more]

PMID: 30813592

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Project description:BackgroundSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, being the primary cause of death from infection, especially if not recognized and treated promptly. The aim of this study was to analyze whether IL-6 rs1800795 polymorphism is associated with septic shock-related death in European white patients who underwent major surgery.MethodsWe performed a retrospective study on 202 septic shock patients who underwent major cardiac or abdominal surgery. The septic shock was established according to the international septic shock definition. The primary outcome variable was the death within 90 days after diagnosis of septic shock. The IL-6 rs1800795 polymorphism was genotyped by Sequenom's MassARRAY platform.ResultsThe median age of the patients was 73 years, 63.4% were male, and more than 40% of patients had heart disease and hypertension. Overall, the survival analysis showed that 111 (55%) patients died with a survival median of 39 days (95% CI 30.7; 47.2). The genetic analysis association with survival was performed under a recessive genetic model (CC vs. GG/CG). Patients with IL-6 rs1800795 CC genotype had higher mortality rate than the IL-6 rs1800795 GG/CG genotype at days 7 [31.6% (6/19) vs. 10.4% (19/183); log-rank test (p = 0.005)] and 28 [57.9% (11/19) vs. 33.3% (61/183); log-rank test (p = 0.009)], and 90 [68.4% (13/19) vs. 53.5% (98/183); log-rank test (p = 0.006)]. The IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death during the first 7 days [adjusted hazard ratio (aHR 4.65; p = 0.002), 28 days (aHR 2.50; p = 0.006), and 90 days (aHR 2.28; p = 0.006)] with septic shock. When patients were stratified by type of surgery, those with IL-6 rs1800795 CC genotype who underwent cardiac surgery had higher risk of death during the first 7 days (aHR 18.39; p = 0.001) and 28 days (aHR 6.1; p = 0.025) than IL-6 rs1800795 GG/GC carrier, whereas patients with IL-6 rs1800795 CC genotype who underwent abdominal surgery had higher risk of death during all follow-up (aHR 1.98; p = 0.050) than IL-6 rs1800795 GG/GC carrier.ConclusionsThe presence of IL-6 rs1800795 CC genotype was associated with higher risk of septic shock-related death in patients who underwent major cardiac or abdominal surgery. These findings need robust validation in bigger independent cohorts.

Dataset Information

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

Publications

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

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