Abstract:
Recognized factors such as severity of the initial injury, age, or the occurrence of complications during the acute hospitalization are imperfect predictors of outcome after TBI (Jennett, Teasdale, et al. 1979; Dikmen, Temkin, et al. 1987; Dikmen, Ross, et al. 1995; Vollmer, Torner, et al. 1991). Recently, the possibility that genetic factors may influence functional outcome after TBI has been supported by the finding from several independent groups that inheritance of the APOE-e4 allele increases the risk of poor neurologic recovery (Teasdale, Nicoll, et al. 1997; Sorbi, Nacmias, et al. 1995; Friedman, Froom, et al. 1999; Jordan, Relkin, et al. 1997). Recent progress in the Human Genome Project has identified common polymorphisms in a number of other genes that have been proposed, on the basis of human and animal studies, to influence the response of neural tissue to injury. Our hypothesis is that inheritance of certain alleles of these polymorphic candidate genes is predictive of a poor neurologic recovery after TBI. Understanding which genes may predispose to poor outcome may be useful in developing tailored therapy to limit damage and improve recovery after traumatic brain injury.

This project has two specific aims:
1) To collect DNA from a population of patients who suffer TBI, as well as prospectively collect information on the severity of injury and functional outcome one year after injury. Patients who suffered moderate or severe TBI will be enrolled in the study, DNA samples collected, and information regarding the initial injury prospectively recorded. Patients will then be contacted 6 months after injury to determine their functional outcome.
2) To determine, using a case-cohort approach, whether inheritance of certain polymorphic alleles is associated with poor outcome after TBI. We will study polymorphisms in nine candidate genes, selected based on their linkage to other neurological diseases that are believed to share pathophysiologic features with TBI, and biologic plausibility of a role in neurodegenerative processes.

It is probable that as understanding of polymorphisms in the human genome advances, more candidate genes will come to our attention and that this well-characterized registry will be a valuable resource for future genetic linkage studies.