The Synergy of ‐260<scp>T T <i>CD14</i></scp> and ‐308<scp>GG <i>TNF‐α</i></scp> Genotypes in Survival of Critically Ill Patients

Fallavena, Paulo Roberto Vargas; Borges, Thalita; Paskulin, Diego D’Ávila; Thurow, Helena Strelow; Paludo, Francis Jackson de Oliveira; Froes, C. dos Santos; Graebin, Pietra; Dias, Fernando Suparregui; Nóbrega, Otávio de Tolêdo; Alho, Clarice Sampaio

doi:10.1111/sji.12002

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…Genetic variations among patients with sepsis have been reported over the past few years [3,4,[29][30][31][32][33][34][35], with major focus on the clotting and innate immune systems, aiming at better understanding possible genetic predispositions for sepsis, sepsisrelated organ dysfunction and death. NK cells are a very important part of the innate immune system, playing a key role during early infection events due to their ability to deliver responses that can lead to effective clearing of pathogens.…”

Section: Discussionmentioning

confidence: 99%

Reduced frequency of two activating KIR genes in patients with sepsis

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Reduced frequency of two activating KIR genes in patients with sepsis

et al. 2017

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“…For the diagnosis of sepsis and septic shock, we used the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria (Levy et al, 2003). Different phenotypic and genotypic information about these patients was found in Paskulin et al (2011), Paludo et al (2013), and Fallavena et al (2013).…”

Section: Phenotypingmentioning

confidence: 99%

More severe clinical course of cardiovascular dysfunction in intensive care unit patients with the 894TT eNOS genotype

Fraga¹,

Paludo²,

Bos³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. The endothelial nitric oxide synthase (eNOS) plays an important homeostatic role in the cardiovascular system (CVS) by maintaining appropriate blood pressure through production of nitric oxide. The 894TT genotype of 894G>T (Glu298Asp, rs1799983), a polymorphic variant of eNOS, has been associated with several vascular diseases. On the basis of this strong relationship, we monitored daily 585 critically ill adult patients according to their degree of CVS dysfunction and investigated their disease progression by the 894G>T genotype. To obtain information of the general population, we obtained the 894G>T eNOS and CVS dysfunction in critically ill patients genotypic and allelic frequencies in a random group of 149 healthy subjects. The patients were genotyped for the eNOS 894G>T polymorphism and daily evaluated according to their degree of CVS dysfunction through the Cardiovascular Sequential Organ Failure Assessment (SOFA) score. The mean value of the global CVS dysfunction score was significantly higher in 894TT patients (1.35 ± 0.57) than in non-894TT patients (1.23 ± 0.37; P = 0.035). This score remained significantly higher in 894TT patients, even in different patient clusters (all patients, septic, and nonseptic patients) during the 1st week at the intensive care unit (1.86 ± 0.8 versus 1.63 ± 0.62, P = 0.005; 2.32 ± 0.10 versus 2.06 ± 0.08, P = 0.009; 0.84 ± 0.09 versus 0.64 ± 0.08, P = 0.027; respectively). This result shows that the mean values of the cardiovascular SOFA score were higher in 894TT patients in all subgroups. The present study provides evidence that the 894TT eNOS genotype is associated with a higher degree of CVS dysfunction in critically ill patients.

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The CD14 rs2569190 TT Genotype Is Associated with an Improved 30-Day Survival in Patients with Sepsis: A Prospective Observational Cohort Study

et al. 2015

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According to previous investigations, CD14 is suggested to play a pivotal role in initiating and perpetuating the pro-inflammatory response during sepsis. A functional polymorphism within the CD14 gene, rs2569190, has been shown to impact the pro-inflammatory response upon stimulation with lipopolysaccharide, a central mediator of inflammation in sepsis. In this study, we hypothesized that the strong pro-inflammatory response induced by the TT genotype of CD14 rs2569190 may have a beneficial effect on survival (30-day) in patients with sepsis. A total of 417 adult patients with sepsis (and of western European descent) were enrolled into this observational study. Blood samples were collected for rs2569190 genotyping. Patients were followed over the course of their stay in the ICU, and the 30-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure as a secondary variable. Moreover, organ support-free days were evaluated as a secondary outcome parameter. TT-homozygous patients were compared to C-allele carriers. Kaplan-Meier survival analysis revealed a higher 30-day mortality risk among C-allele carriers compared with T homozygotes (p = 0.0261). To exclude the effect of potential confounders (age, gender, BMI and type of infection) and covariates that varied at baseline with a p-value < 0.2 (e.g., comorbidities), we performed multivariate Cox regression analysis to examine the survival time. The CD14 rs2569190 C allele remained a significant covariate for the 30-day mortality risk in the multivariate analysis (hazard ratio, 2.11; 95% CI, 1.08-4.12; p = 0.0282). The 30-day mortality rate among C allele carriers was 23%, whereas the T homozygotes had a mortality rate of 13%. Additionally, an analysis of organ-specific SOFA scores revealed a significantly higher SOFA-Central nervous system score among patients carrying the C allele compared with T-homozygous patients (1.9±1.1 and 1.6±1.0, respectively; p = 0.0311). In conclusion, CD14 rs2569190 may act as a prognostic variable for the short-term outcome (30-day survival) in patients with sepsis.

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The Synergy of ‐260T T CD14 and ‐308GG TNF‐α Genotypes in Survival of Critically Ill Patients

Cited by 3 publications

References 42 publications

Reduced frequency of two activating KIR genes in patients with sepsis

Reduced frequency of two activating KIR genes in patients with sepsis

More severe clinical course of cardiovascular dysfunction in intensive care unit patients with the 894TT eNOS genotype

The CD14 rs2569190 TT Genotype Is Associated with an Improved 30-Day Survival in Patients with Sepsis: A Prospective Observational Cohort Study

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