Genetic Variation Affects Recovery From Concussion Interview with:

Dr. Jane McDevitt Temple University in Philadelphia

Dr. Jane McDevitt

Dr. Jane McDevitt
Temple University in Philadelphia What is the background for this study?

Dr. McDevitt: During a head impact there is a mechanical load that causes acceleration and deceleration forces on the brain within the cranium. The acceleration and deceleration causes stress to the neurons and initiates a neurometabolic cascade, where excitatory neurotransmitters such as glutamate are released and depolarize the cell. This triggers protein channels to open and allow ions into and out of the cell. Increases in calcium persist longer and have greater magnitude of imbalance than any other ionic disturbance. One channel responsible for allowing calcium into the cell is r-type voltage-gated calcium channel. One of the main proteins within this voltage-gated calcium channel is the CACNA1E protein produced by the CACNA1E gene. This protein forms the external pore and contains a pair of glutamate residues that are required for calcium selectivity. It is also responsible for modulating neuronal firing patterns. A variation within this gene (i.e,CACNA1E ) that regulates expression levels of CACNA1E could be associated with how an athlete recovers following a concussion injury.

Upwards of 20% of the concussed population fall into the prolonged recovery category, which puts these athletes at risk for returning to play quicker than they should. Variation in recovery depends on extrinsic factors like magnitude of impact, and sport, or intrinsic factors like age or sex. One intrinsic factor that has not been definitively parsed out is genetic variation. Recovery is likely to be influenced by genetics because genes determine the structure and function of proteins involved in the cell’s resistance and response to mechanical stress. Due to CACNA1E’s relationship to calcium influx regulation, a single nucleotide polymorphism (SNP) could modify the expression level of the protein responsible for regulating calcium. Altered protein levels could lead to athlete’s responding to concussive injuries differently. The main objective of this study was to examine the association between CACNA1E SNPs with concussion recovery in athletes. What are the main findings?

Dr. McDevitt: We found that carries of the GG genotype were 5 times more likely to have prolonged recovery compared to those carrying the AA or GA genotype. This could be due to the G (guanine) to A (adenine) missense SNP found in CACNA1E gene that changes an alanine amino acid to threonine amino acid. Studies have found that genetic variations that alter the amino acid sequence cause different effects or phenotypes. What is the background for this study? What are the main findings?

Dr. McDevitt: Using the information from this study, clinicians can utilize genotyping procedures during the pre-season physical examinations to identify which individuals are predisposed to a prolonged recovery, which could improve the concussion monitoring and concussion management. What should clinicians and patients take away from your report?

Dr. McDevitt: We will continue to investigate other SNPs in gene that are involved with producing proteins that have major roles in the neurometabolic cascade. Additionally, we are continuing to grow our DNA bank to have larger cohorts, and we are working on grant submissions to look at if these genetic polymorphisms cause increases or decreases in the proteins to further validate our findings. Thank you for your contribution to the community.


Abstract presented at the American Orthopaedic Society for Sports Medicine’s (AOSSM) Specialty Day March 2016

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Dr. Jane McDevitt (2016). Genetic Variation Affects Recovery From Concussion