(Verbatim from the aplicant's abstract) This is a new application for support of a small-scale collaborative research project entitled """"""""Genetic Predisposition to Severe Sepsis."""""""" The long-term (two cycle) objective of this project is to determine the relationships among genetic markers, specific gene expression and severe sepsis in the United States population. Understanding these relationships will allow for risk assessment and for targeted monitoring of critically ill patients and also for risk stratification in the design of clinical trials of new sepsis therapies. The goal for the first four-year cycle of the application is to determine allele frequency of certain genetic markers and assess their association with predisposition to severe sepsis and outcome following severe sepsis.
The specific aims that will be achieved to attain the goal are: (1) Establish an ethical process for anonymized collection of demographic, clinical, outcome and genetic data from a heterogeneous and ethnically diverse population of critically ill patients: (2) Determine allelotype distribution of N-l2 markers in the septic population and in appropriately matched controls; (3) Determine the markers associated with genetic predisposition to severe sepsis; and (4) Estimate the predictive value of these markers upon outcome from severe sepsis. In order to accomplish tEe specific aims, data will be obtained prospectively from anonymized critically ill patients admitted to intensive care units participating the Society of Critical Care Medicine's Project IMPACT. Discarded blood from those patients will be allelotyped using high throughput analytic techniques at a set of markers that preliminary studies suggest are relevant to predisposition to, and Outcome from, severe sepsis. The project meets the confidentiality and specimen access requirements typical of an NIH Human Tissue Repository.
| Watanabe, Eizo; Zehnbauer, Barbara A; Oda, Shigeto et al. (2012) Tumor necrosis factor -308 polymorphism (rs1800629) is associated with mortality and ventilator duration in 1057 Caucasian patients. Cytokine 60:249-56 |
| Watanabe, Eizo; Buchman, Timothy G; Hirasawa, Hiroyuki et al. (2010) Association between lymphotoxin-alpha (tumor necrosis factor-beta) intron polymorphism and predisposition to severe sepsis is modified by gender and age. Crit Care Med 38:181-93 |
