DNA methylation of a NF-κB binding site in the aquaporin 5 promoter impacts on mortality in sepsis.

摘要: Altered aquaporin 5 (AQP5) expression in immune cells impacts on key mechanisms of inflammation and is associated with sepsis survival. Since epigenetic regulation via DNA methylation might contribute to a differential AQP5 sepsis, we tested the hypotheses that promotor (1) influences expression, (2) 30-day survival septic patients, (3) alters nuclear transcription factor NF-κB binding. mRNA was quantified by real-time PCR whole blood samples 135 patients. In silico computer analysis promoter (nt-567 nt-975) revealed seven putative inflammatory binding sites these analyzed. Electrophoretic mobility shift assays were performed assess region nt-937. After adjustment for multiple testing, greater rate found at cytosine site nt-937 linked non-survivors compared survivors (p = 0.002, padj = 0.014). This (p = 0.037). Greater (≥16%) also an independently increased risk death within 30 days (HR: 3.31; 95% CI: 1.54–6.23; p = 0.002). We detected functionally important (nt-937) inflammatorily acting NF-κB, non-survivors. Thus, APQ5 methylation, presumably related binding, prognostically relevant demonstrates changes impact outcome.