VARIANTS IN NFB-INDUCING KINASE GENE (NIK, MAP3K14) ASSOCIATED WITH MORTALITY IN SEPTIC SHOCK

Septic shock is the most common cause of death in critically ill patients in Intensive Care Units. The development of septic shock is an extremely complex process involving many different cellular pathways of interacting proteins. One of the main proteins involved in these pathways is called nuclear factor kappa beta (NFκB). This protein controls the activities of other genes that are important to the survival of patients with septic shock. NFκB activity is controlled by another protein called NFκB inducing kinase (NIK).

Even though human DNA code is ~99.8% similar between people, small differences from person to person have been shown to affect outcome in disease and response to medicine, a field called pharmacogenetics. We have found an association with one of these DNA differences in NIK and increased mortality in approximately 1200 patients, meaning that depending on your genetic code in this gene you may have a better or worse chance of surviving sepsis. This research project would allow us to determine exactly how NIK genetic variation affects the NIK protein and thus the chance of dying from septic shock, which may also lead to better treatment for patients in intensive care units.

Faculty Supervisor:

Dr. Keith Walley

Student:

Simone Thair

Partner:

Sirius Genomics Inc.

Discipline:

Medicine

Sector:

Life sciences

University:

University of British Columbia