Genetic Polymorphisms in Sepsis

Abstract The number of genetic polymorphisms shown to play a role in sepsis continues to increase. At the same time, platforms for genetic sequencing and expression analysis are being refined, allowing unprecedented data generation. International databases may soon facilitate synchrony of genotypic and phenotypic data using enormous numbers of septic patients. If this occurs, 2 strategies for investigating polymorphisms in sepsis are likely to gain favor. In the first strategy, sepsis will continue to be viewed as a single entity. High-throughput genetic techniques will be used to evaluate numerous polymorphisms, each with fractional disease responsibility. Nongenetic variables, such as pathogen characteristics, underlying host medical conditions, and type and timing of resuscitation, will be considered cofactors. Using this approach, principal components that predict susceptibility to and outcomes during sepsis are likely to be identified. In the second strategy, sepsis will be divided into subtypes based on the concentration of specific variables. Categories will be based on features like the presence or absence of specific polymorphisms, gram-positive or gram-negative staining of causative organisms, age and comorbid conditions of the host, recent administration of chemotherapeutic agents, and hospital setting (ie, community vs teaching institution). Each category will be used to create homogenous sepsis subgroups for detailed evaluation. This approach will increase the odds of finding single dominant factors responsible for predilection and/or outcome within well-defined groups among those with sepsis. Several elements will be essential for the success of both these strategies. Firstly, databases that are extremely detailed will have to be generated. Secondly, better clinical information technology systems will be needed to facilitate large-scale phenotyping. Thirdly, standardization of protocols will need to take place to ensure uniformity of data sets. If the rapid advances in technology and informatics continue, they may catalyze paradigm shifts with regard to how clinicians address sepsis. Clinicians may change their focus from aggressive uniform treatment strategies to rapid stratification and subcategorization, with subsequent aggressive targeted therapeutic interventions. Advances in technology have the potential to change our primary goal in sepsis from rapid treatment to prevention for those most at risk. The cost savings to the US health care systems from such changes could be substantial.