A study in the January 2013 issue of Anesthesiology offers evidence that variations in what is called the NFKB gene could play an important role in helping to determine the survival rate of patients who acquire sepsis, a condition in which the body is overwhelmed by infection, and which is the leading cause of death in hospitals.
"Wide variability exists regarding the outcome of patients with severe sepsis, and some of the variability regarding the risk of dying could be caused by genetic variations," said lead study author Michael Adamzik, M.D., Associate Professor, Department of Anesthesiology and Intensive Care Medicine, University Duisberg-Essen, Essen, Germany. "Our study unravels the molecular mechanism by which a common genetic variation in the regulation region of the NFKB gene may amplify and perpetuate inflammation and infection due to sepsis."
Using blood from human subjects, Dr. Adamzik and his research team found that patients with a specific genetic variation (58 percent of the study group) showed, after infection, a two-fold increase of a subunit protein called NFKB-1 and more inflammation compared to patients with other genotypes.
The NFKB genetic pathway is believed to be responsible for amplifying inflammation that takes place in sepsis. Dr. Adamzik's study seems to indicate that the protein NFKB-1, specifically, could affect the key mechanism of sepsis and possibly influence patient survival rates.
"This genetic variation turned out to represent both an important and independent predictor of mortality in our patients," said Simon Schäfer, M.D., Research Assistant, Department of Anesthesiology and Intensive Care Medicine, University Duisberg-Essen. "Patients with one genetic variant were associated with an almost two-fold greater risk for death during sepsis. Our study showed for the first time that this genetic variation markedly increases inflammation and influences the risk of dying from sepsis."
Dr. Adamzik stated that future studies should work to unravel whether anti-inflammatory sepsis treatment should be adjusted in patients according to their genotype.
- Michael Adamzik, Simon Schäfer, Ulrich H. Frey, Arne Becker, Maximiliane Kreuzer, Sandra Winning, Stilla Frede, Jörg Steinmann, Joachim Fandrey, Kai Zacharowski, Winfried Siffert, Jürgen Peters, Matthias Hartmann. The NFKB1 Promoter Polymorphism (−94ins/delATTG) Alters Nuclear Translocation of NF-κB1 in Monocytes after Lipopolysaccharide Stimulation and Is Associated with Increased Mortality in Sepsis. Anesthesiology, 2013; 118 (1): 123 DOI: 10.1097/ALN.0b013e318277a652
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