Genetic risk factors for concussion, concussion severity, and neurocognitive recovery from concussion in college football and soccer players.

Project Title: Genetic risk factors for concussion, concussion severity, and neurocognitive recovery from concussion in college football and soccer players.

Investigators, Title, Institution, and Role on Project: Thomas Terrell, M.D., M.Phil. Florida State University School of Medicine, Daytona Beach, FL

Jeffrey Barth, PhD, University of Virginia, Charlottesville, VA, Co-Investigator

Ellen Bennett, PhD, Duke University, Dept of Neurology, Molecular Biology Lab, Durham, NC, Co-Investigator

Robert Cantu, MD, Emerson Hospital, Concord, MA, Co-Investigator

Doug McKeag, MD, University of Indiana School of Medicine, Indianapolis, IN, Co-Investigator

Daniel Laskowitz, MD, PhD, Dept of Neurology, Durham, NC, Co-Investigator

Ambesaw Selassie, PhD, Medical University of South Carolina, Charleston, SC, Statistician

Ruth Abramson, PhD, Univ. of South Carolina School of Public Health, Columbia, SC, Co-Investigator

Roberd Bostick, MD, MSc, Emory University School of Public Health, Atlanta, GA

Background: The genetic susceptibility to mild TBI (concussion) in athletes is poorly studied and understood but an important area of research. The post-TBI recovery of severe TBI victims is worse if they possess the APOE e4 genotype (Friedman et al., 1999). Two small studies of pro football players and boxers have suggested a possible association of APOE e4 with lower neurocognitive scores in individuals with multiple concussions (Kutner et al. 2002; Jordan et al., 1999). No prospective study has investigated the association of genetic polymorphisms with risk of concussion, multiple concussions, more severe concussions, or an incomplete or slower rate of neurocognitive recovery.

The proposed project began as a 2 year cross-sectional study followed by an ongoing 2 year pilot prospective cohort study. The cross sectional study based on 176 college football/soccer athletes demonstrated a statistically significant increased risk of a history of self reported concussion for the APOE promoter G-219T TT genotype relative to the GG genotype (OR, 2.8; 95% CI, 1.1 to 6.9), after adjustment for age, sport, school, and years in their primary sport (Terrell et al., 2008). Due to inadequate n, there was no association with APOE genotypes.

Goals and Aims:We propose a multi-center prospective cohort study to determine if genetic polymorphisms such as APOE, APOE promoter G219T, and tau gene exon 6(Ser53Pro and His47Tyr), tumor necrosis factor alpha, and IL-6 are associated with an increased risk of concussion, more severe concussion, slowed or incomplete neurocognitive recovery, and permanent neurocognitive deficits in college football and college soccer players of both genders.

Compare and define the neurcognitive recovery of concussed male/female soccer players by gender, genotype, and other covariates.

Methods:This prospective multi-center study at 20 universities will follow football and male and female college soccer players for 2 years. Athletes will complete baseline concussion/med history questionnaires, the Standardized Assessment of Concussion (SAC), genetic sampling with a mouth swab, and baseline computerized NP testing with the Concussion Resolution Index (CRI; Headminder). Study variables include sport, position, number of years playing sport, helmet type, scholastic attainment, characteristics of concussion, and others. Football/soccer athletes will be followed until they experience a concussion. Post-concussion SAC scores and NP testing using CRI at 24 hrs, 5, 7 and 14 days will be obtained and compared to baseline measures.

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