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. Conclusion 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.