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

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.

[1]  Jinhua Xu,et al.  Association of TNFAIP3 and TNIP1 polymorphisms with systemic lupus erythematosus risk: A meta-analysis. , 2018, Gene.

[2]  M. Levy,et al.  Surviving sepsis campaign: research priorities for sepsis and septic shock , 2018, Intensive Care Medicine.

[3]  M. Rizk,et al.  Association of Tumor Necrosis Factor Alpha-Induced Protein 3 Interacting Protein 1 (TNIP1) Gene Polymorphism (rs7708392) with Lupus Nephritis in Egyptian Patients , 2018, Biochemical Genetics.

[4]  A. Kawasaki,et al.  Association of a single nucleotide polymorphism in TNIP1 with type-1 autoimmune hepatitis in the Japanese population , 2018, Journal of Human Genetics.

[5]  A. Alvaro-Meca,et al.  Epidemiological trends of sepsis in the twenty-first century (2000–2013): an analysis of incidence, mortality, and associated costs in Spain , 2018, Population Health Metrics.

[6]  C. Coopersmith,et al.  The intestinal microenvironment in sepsis. , 2017, Biochimica et biophysica acta. Molecular basis of disease.

[7]  N. Matsuda,et al.  Recent advances in the pathophysiology and molecular basis of sepsis‐associated organ dysfunction: Novel therapeutic implications and challenges , 2017, Pharmacology & therapeutics.

[8]  G. Boccia,et al.  Sepsis and septic shock: New definitions, new diagnostic and therapeutic approaches. , 2017, Journal of global antimicrobial resistance.

[9]  J. Russell,et al.  Update of Sepsis in the Intensive Care Unit , 2017, Journal of Innate Immunity.

[10]  C. Deutschman.  "Defining" Sepsis: Moving Toward Measuring the "Dysregulated Host Response". , 2017, Critical care medicine.

[11]  J. Syrjänen,et al.  Sepsis-related mortality in 497 cases with blood culture-positive sepsis in an emergency department. , 2017, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[12]  Huiqing Sun,et al.  Three single nucleotide polymorphisms of TNFAIP3 gene increase the risk of rheumatoid arthritis , 2017, Oncotarget.

[13]  M. Delano,et al.  The immune system's role in sepsis progression, resolution, and long‐term outcome , 2016, Immunological reviews.

[14]  F. Gilsanz,et al.  Epidemiologic trends of sepsis in western countries. , 2016, Annals of translational medicine.

[15]  C. Coopersmith,et al.  Mechanisms of Intestinal Barrier Dysfunction in Sepsis , 2016, Shock.

[16]  Yuan Yuan,et al.  SNP-SNP Interaction between TLR4 and MyD88 in Susceptibility to Coronary Artery Disease in the Chinese Han Population , 2016, International journal of environmental research and public health.

[17]  R. Bellomo,et al.  The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). , 2016, JAMA.

[18]  D. Ochoa,et al.  Polymorphisms Associated with Age at Onset in Patients with Moderate-to-Severe Plaque Psoriasis , 2015, Journal of immunology research.

[19]  E. V. van Lieshout,et al.  Effects of Sequence Variations in Innate Immune Response Genes on Infectious Outcome in Trauma Patients: A Comprehensive Review , 2015, Shock.

[20]  M. Juan,et al.  Association of Polymorphisms in IRAK1, IRAK4 and MyD88, and Severe Invasive Pneumococcal Disease , 2015, The Pediatric infectious disease journal.

[21]  P. Gaffney,et al.  Review: A20‐Binding Inhibitor of NF‐κB Activation 1 Is a Physiologic Inhibitor of NF‐κB: A Molecular Switch for Inflammation and Autoimmunity , 2015, Arthritis & rheumatology.

[22]  R. Veach,et al.  New paradigms in sepsis: from prevention to protection of failing microcirculation , 2015, Journal of thrombosis and haemostasis : JTH.

[23]  J. Chiche,et al.  Timing and causes of death in septic shock , 2015, Annals of Intensive Care.

[24]  A. Peitzman,et al.  X Chromosome-Linked IRAK-1 Polymorphism Is a Strong Predictor of Multiple Organ Failure and Mortality Postinjury , 2014, Annals of surgery.

[25]  A. Kijlstra,et al.  Association of a TNIP1 Polymorphism with Vogt-Koyanagi-Harada Syndrome but Not with Ocular Behcet’s Disease in Han Chinese , 2014, PloS one.

[26]  Pål Sætrom,et al.  Circular RNAs are depleted of polymorphisms at microRNA binding sites , 2014, Bioinform..

[27]  You Li,et al.  The Functional Polymorphisms of miR-146a Are Associated with Susceptibility to Severe Sepsis in the Chinese Population , 2014, Mediators of inflammation.

[28]  P. Brown,et al.  Correction: Cell-Type Specific Features of Circular RNA Expression , 2013, PLoS Genetics.

[29]  R. Jonsson,et al.  Association of Genes in the NF‐κB Pathway with Antibody‐Positive Primary Sjögren's Syndrome , 2013, Scandinavian journal of immunology.

[30]  R. K. Oliver,et al.  ABIN1 dysfunction as a genetic basis for lupus nephritis. , 2013, Journal of the American Society of Nephrology : JASN.

[31]  P. Gaffney,et al.  Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome , 2013, Nature Genetics.

[32]  Julia Salzman,et al.  Cell-Type Specific Features of Circular RNA Expression , 2013, PLoS genetics.

[33]  Jae-Hoon Chang,et al.  Regulation of nuclear factor-κB in autoimmunity. , 2013, Trends in immunology.

[34]  C. Sprung,et al.  Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock 2012 , 2013, Critical care medicine.

[35]  P. Gaffney,et al.  Association of two independent functional risk haplotypes in TNIP1 with systemic lupus erythematosus. , 2012, Arthritis and rheumatism.

[36]  M. Fredrikson,et al.  Genetic variation and alterations of genes involved in NFκB/TNFAIP3- and NLRP3-inflammasome signaling affect susceptibility and outcome of colorectal cancer. , 2012, Carcinogenesis.

[37]  A. Ma,et al.  A20: linking a complex regulator of ubiquitylation to immunity and human disease , 2012, Nature Reviews Immunology.

[38]  A. Barton,et al.  Rheumatoid Arthritis-associated Polymorphisms at 6q23 Are Associated with Radiological Damage in Autoantibody-positive RA , 2012, The Journal of Rheumatology.

[39]  C. Bai,et al.  Genetic variation in the TNF receptor-associated factor 6 gene is associated with susceptibility to sepsis-induced acute lung injury , 2012, Journal of Translational Medicine.

[40]  Jane Worthington,et al.  Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study , 2012, Annals of the rheumatic diseases.

[41]  B. Aneskievich,et al.  Emerging roles for TNIP1 in regulating post-receptor signaling. , 2012, Cytokine & growth factor reviews.

[42]  S. Bae,et al.  Associations between TNFAIP3 gene polymorphisms and rheumatoid arthritis: a meta-analysis , 2012, Inflammation Research.

[43]  T. Nakajima,et al.  A single nucleotide polymorphism in the 3′-untranslated region of MyD88 gene is associated with Buerger disease but not with Takayasu arteritis in Japanese , 2011, Journal of Human Genetics.

[44]  Chenling Yao,et al.  Variants in the Toll-interacting protein gene are associated with susceptibility to sepsis in the Chinese Han population , 2011, Critical care.

[45]  Gerald McGwin,et al.  A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus , 2009, Nature Genetics.

[46]  J. Todd,et al.  Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus , 2009, Genes and Immunity.

[47]  David Altshuler,et al.  Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus , 2008, Nature Genetics.

[48]  E. Abraham,et al.  Variant IRAK-1 haplotype is associated with increased nuclear factor-kappaB activation and worse outcomes in sepsis. , 2006, American journal of respiratory and critical care medicine.

[49]  A. Malik,et al.  NF-κB activation as a pathological mechanism of septic shock and inflammation , 2006 .

[50]  M. Levy,et al.  2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference , 2003, Intensive care medicine.

[51]  Djillali Annane,et al.  Reducing mortality in sepsis: new directions , 2002, Critical care.

[52]  C. Sprung,et al.  The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study , 1999, Intensive Care Medicine.

[53]  W. Knaus,et al.  APACHE II: a severity of disease classification system. , 1985 .

[54]  L. Catrysse,et al.  A20 in inflammation and autoimmunity. , 2014, Trends in immunology.

[55]  N. Kawada,et al.  The *1244 A>G polymorphism of MyD88 (rs7744) is closely associated with susceptibility to ulcerative colitis. , 2014, Molecular medicine reports.

[56]  Chenling Yao,et al.  Association of genetic variants in the IRAK-4 gene with susceptibility to severe sepsis. , 2012, World journal of emergency medicine.

[57]  Gangqiao Zhou,et al.  TRAF6 polymorphisms not associated with the susceptibility to and severity of sepsis in a Chinese population. , 2010, World journal of emergency medicine.

[58]  A. Malik,et al.  NF-kappa B activation as a pathological mechanism of septic shock and inflammation. , 2006, American journal of physiology. Lung cellular and molecular physiology.