title: Aquaporin 5 gene promoter--1364A/C polymorphism associated with 30-day survival in severe sepsis.
abstract: BACKGROUND
  Because the aquaporin (AQP) 5 promoter -1364A/C polymorphism is associated with altered AQP5 expression, this association could have an impact on key mechanisms in sepsis, such as cell migration, activity of the rennin-angiotensin- aldosterone system (RAAS), and water transport across biologic membranes. Therefore, we tested the hypothesis that the AQP5 promoter -1364A/C polymorphism is associated with increased 30-day survival in severe sepsis.
  
  
  METHODS
  In a prospective study, adults with severe sepsis (N = 154) were genotyped for the AQP5 promoter -1364A/C polymorphism. The clinical endpoint was 30-day survival. Kaplan-Meier plots and multivariate proportional hazard analyses were used to evaluate the relationship between genotypes and clinical outcomes.
  
  
  RESULTS
  Thirty-day survival was significantly associated with AQP5 -1364A/C genotypes (P = 0.001). Survival rates were 57% for AA genotypes (n = 90) but 83% for combined AC/CC genotypes (56 vs. 8, respectively). Multivariate proportional hazard analysis including sex, age, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment score, body mass index, necessity for continuous hemofiltration/dialysis, concentrations of plasma angiotensin II, serum aldosterone, C-reactive protein, and interleukin 6 as covariates revealed the AQP5 -1364A/C polymorphism as a strong and independent prognostic factor for 30-day survival. In this analysis, homozygous AA subjects were at high risk for death within 30 days (hazard ratio, 3.59; 95% CI, 1.47-8.80; P = 0.005) compared with AC/CC genotypes.
  
  
  CONCLUSIONS
  The C-allele of the AQP5 -1364A/C polymorphism is associated with increased 30-day survival in patients with severe sepsis. This finding suggests the importance of variations in expression of AQP5 channels in severe sepsis.
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Hufelandstr. 55, D-45122 Essen, Germany. michael.adamzik@uk-essen.de
authors.forename: Michael
authors.initials: M
authors.lastname: Adamzik
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Frey
authors.forename: Stephan
authors.initials: S
authors.lastname: Möhlenkamp
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.forename: Christian
authors.initials: C
authors.lastname: Waydhas
authors.forename: Günther
authors.initials: G
authors.lastname: Marggraf
authors.forename: Marc
authors.initials: M
authors.lastname: Dammann
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinmann
authors.forename: Winfried
authors.initials: W
authors.lastname: Siffert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D051402:Aquaporin 5 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D018805:Sepsis / Q000235:genetics* / Q000401:mortality*
chemical_list: D051402:Aquaporin 5