title: Higher frequency of septic shock in septic patients with the 47C allele (rs4880) of the SOD2 gene.
abstract: OBJECTIVE
  To analyze the effect of the two different versions of the manganese superoxide dismutase gene (SOD2) on sepsis. The SOD2 gene presents the 47C>T single nucleotide polymorphism (SNP; ID: rs4880) which produces MnSOD with different activities. The -9Val MnSOD (47T allele) is less efficient than the -9Ala version (47C allele). During sepsis there are abundance of ROS, high SOD2 expression and excess of H(2)O(2) synthesis. High concentrations of H(2)O(2) could affect the sepsis scenario and/or the sepsis outcome.
  
  
  METHODS
  We determined the 47C>T single nucleotide polymorphism (SNP) frequencies in 529 critically ill patients with or without sepsis, facing outcome. To collect information on population frequencies, we obtained a pilot 47C>T genotypic and allelic frequencies in a random group of 139 healthy subjects.
  
  
  RESULTS
  We compared the 47C allele carriers (47CC+47CT genotypes) with 47TT homozygotes and noticed a significant association between 47C allele carriers and septic shock in septic patients (P=0.025). With an adjusted binary multivariate logistic regression, incorporating 47C>T SNP and the main clinical predictors, we showed high SOFA scores [P<0.001, OR=9.107 (95% CI=5.319-15.592)] and 47C allele [P=0.011, OR=2.125 (95% CI=1.190-3.794)] were significantly associated with septic shock outcome. With this information we presented a hypothesis suggesting that this negative outcome from sepsis is possibly explained by effects on cellular stress caused by 47C allele.
  
  
  CONCLUSIONS
  In our population there was a significant higher frequency of septic shock in septic patients with the 47C allele of the SOD2 gene. This higher 47C allele frequency in septic patients with negative outcome could be explained by effects of higher activity MnSOD on cellular stress during the sepsis.
authors.affiliation: FABIO-PUCRS, Brazil. francisjop@yahoo.com.br
authors.forename: Francis Jackson de Oliveira
authors.initials: FJ
authors.lastname: Paludo
authors.forename: Juliane Bentes
authors.initials: JB
authors.lastname: Picanço
authors.forename: Paulo Roberto Vargas
authors.initials: PR
authors.lastname: Fallavena
authors.forename: Lucas da Rosa
authors.initials: Lda R
authors.lastname: Fraga
authors.forename: Pietra
authors.initials: P
authors.lastname: Graebin
authors.forename: Otávio de Toledo
authors.initials: Ode T
authors.lastname: Nóbrega
authors.forename: Fernando Suparregui
authors.initials: FS
authors.lastname: Dias
authors.forename: Clarice Sampaio
authors.initials: CS
authors.lastname: Alho
mesh_terms: D016022:Case-Control Studies; D016638:Critical Illness; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D012772:Shock, Septic / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2