title: TNF -308G > a promoter polymorphism (rs1800629) and outcome from critical illness.
abstract: BACKGROUND
  The susceptibility to adverse outcome from critical illness (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. An over expression of tumor necrosis factor alpha (TNF-α) can lead to the progression of the inflammatory condition.
  
  
  OBJECTIVE
  We assessed the relationship of the genotype distribution of -308G >A TNF-α polymorphism with regard to the development of sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients.
  
  
  METHODS
  Observational, hospital-based cohort study of 520 critically ill Caucasian patients from southern Brazil admitted to the general ICU of São Lucas Hospital, Porto Alegre, Brazil. Patients were monitored daily from the ICU admission day to hospital discharge or death, measuring SOFA score, sepsis, and septic shock occurrences. The -308G >A TNF-α SNP effect was analyzed in the entire patient group, in patients with sepsis (349/520), and in those who developed septic shock (248/520).
  
  
  RESULTS
  The genotypic and allelic frequencies were -308GG = 0.72; -308GA = 0.27; -308AA = 0.01; -308G = 0.85; -308A = 0.15. No associations were found with sepsis, septic shock, organ dysfunction, and/or mortality rates among the TNF-α genotypes. Our results reveal that the -308G >A TNF-α SNP alone was not predictive of severe outcomes in critically ill patients.
  
  
  CONCLUSIONS
  The principal novel input of this study was the larger sample size in an investigation with -308G > A TNF-α SNP. The presence of -308A allele is not associated with sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients.
authors.affiliation: Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Diego D'Ávila
authors.initials: DD
authors.lastname: Paskulin
authors.forename: Paulo Rv
authors.initials: PR
authors.lastname: Fallavena
authors.forename: Francis Jo
authors.initials: FJ
authors.lastname: Paludo
authors.forename: Thiago J
authors.initials: TJ
authors.lastname: Borges
authors.forename: Juliane B
authors.initials: JB
authors.lastname: Picanço
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Dias
authors.forename: Clarice Sampaio
authors.initials: CS
authors.lastname: Alho
mesh_terms: D015331:Cohort Studies; D016638:Critical Illness; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D009102:Multiple Organ Failure / Q000235:genetics / Q000401:mortality*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D018805:Sepsis / Q000235:genetics / Q000401:mortality*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha