Genetic Factors Linked to Slow Concussion Recovery in Athletes

SEATTLE—An investigation into the association of the (GT)n variable nucleotide tandem repeats (VNTR) within the GRIN2A gene and concussion recovery found that athletes carrying the long allele genotype are predisposed to prolonged recovery following a concussive injury. The findings were presented at the 2014 Annual Meeting of the American Orthopaedic Society for Sports Medicine.

“We identified that patients with a long allele in the (GT)n genotype were four times more likely to have a prolonged concussion recovery,” said lead author Jane McDevitt, PhD, from Temple University in Philadelphia, Pennsylvania, and her research colleagues.

Fifty-one athletes with a diagnosed concussion from a hospital concussion program completed a standardized initial evaluation. Concussion injury characteristics and acute signs and symptoms were assessed, followed by an objective screening that included vestibular ocular assessments, the BESS test, and an ImPACT exam.

Participants provided salivary samples for isolation of DNA. The number of (GT) VNTR within the promoter region of GRIN2A was genotyped. The long (L) allele was defined as an allele with 25 or more dinucleotide repeats in the GT tract. The short (S) allele was defined as an allele with < 25 dinucleotide repeats in the GT tract.

Based on the results of genetic analysis, participants were genotyped as LL homozygotes, SS homozygotes, or LS heterozygotes. Participants’ concussion recovery time was followed prospectively until the full return to play clearance date determined by the treating physician.

Participant’s recovery time was categorized as normal (≤ 20 days) or prolonged (> 20 days). The DNA region surrounding position (-975 to -776) in the promoter of GRIN2A was amplified by PCR, and was analyzed by capillary electrophoresis. Fragment length polymorphism analysis was performed by measuring the migration time of a PCR product, and extrapolation to the known fragments in the DNA standard ladder using computer software. The number of GT dinucleotide repeats was calculated using the following equation: n(GT)=(L -167)/2, where L is the length of the PCR fragment estimated in base pairs.

Results indicated there was a significant association between the GT VNTR (recessive model: LL versus SS + LS) and recovery, where the chance of prolonged recovery was 4.3 times greater for homozygous carriers of the long allele.

“Making the genetic connection in this data is an exciting step for concussion injury research,” said Dr. McDevitt. “Knowing this information could help improve monitoring and management of athletes who experience concussion, and may also aid in the development of genetic counseling in athletes exposed to concussive head impacts.”

SEATTLE—An investigation into the association of the (GT)n variable nucleotide tandem repeats (VNTR) within the GRIN2A gene and concussion recovery found that athletes carrying the long allele genotype are predisposed to prolonged recovery following a concussive injury. The findings were presented at the 2014 Annual Meeting of the American Orthopaedic Society for Sports Medicine.

“We identified that patients with a long allele in the (GT)n genotype were four times more likely to have a prolonged concussion recovery,” said lead author Jane McDevitt, PhD, from Temple University in Philadelphia, Pennsylvania, and her research colleagues.

Fifty-one athletes with a diagnosed concussion from a hospital concussion program completed a standardized initial evaluation. Concussion injury characteristics and acute signs and symptoms were assessed, followed by an objective screening that included vestibular ocular assessments, the BESS test, and an ImPACT exam.

Participants provided salivary samples for isolation of DNA. The number of (GT) VNTR within the promoter region of GRIN2A was genotyped. The long (L) allele was defined as an allele with 25 or more dinucleotide repeats in the GT tract. The short (S) allele was defined as an allele with < 25 dinucleotide repeats in the GT tract.

Based on the results of genetic analysis, participants were genotyped as LL homozygotes, SS homozygotes, or LS heterozygotes. Participants’ concussion recovery time was followed prospectively until the full return to play clearance date determined by the treating physician.

Participant’s recovery time was categorized as normal (≤ 20 days) or prolonged (> 20 days). The DNA region surrounding position (-975 to -776) in the promoter of GRIN2A was amplified by PCR, and was analyzed by capillary electrophoresis. Fragment length polymorphism analysis was performed by measuring the migration time of a PCR product, and extrapolation to the known fragments in the DNA standard ladder using computer software. The number of GT dinucleotide repeats was calculated using the following equation: n(GT)=(L -167)/2, where L is the length of the PCR fragment estimated in base pairs.

Results indicated there was a significant association between the GT VNTR (recessive model: LL versus SS + LS) and recovery, where the chance of prolonged recovery was 4.3 times greater for homozygous carriers of the long allele.

“Making the genetic connection in this data is an exciting step for concussion injury research,” said Dr. McDevitt. “Knowing this information could help improve monitoring and management of athletes who experience concussion, and may also aid in the development of genetic counseling in athletes exposed to concussive head impacts.”

SEATTLE—An investigation into the association of the (GT)n variable nucleotide tandem repeats (VNTR) within the GRIN2A gene and concussion recovery found that athletes carrying the long allele genotype are predisposed to prolonged recovery following a concussive injury. The findings were presented at the 2014 Annual Meeting of the American Orthopaedic Society for Sports Medicine.

“We identified that patients with a long allele in the (GT)n genotype were four times more likely to have a prolonged concussion recovery,” said lead author Jane McDevitt, PhD, from Temple University in Philadelphia, Pennsylvania, and her research colleagues.

Fifty-one athletes with a diagnosed concussion from a hospital concussion program completed a standardized initial evaluation. Concussion injury characteristics and acute signs and symptoms were assessed, followed by an objective screening that included vestibular ocular assessments, the BESS test, and an ImPACT exam.

Participants provided salivary samples for isolation of DNA. The number of (GT) VNTR within the promoter region of GRIN2A was genotyped. The long (L) allele was defined as an allele with 25 or more dinucleotide repeats in the GT tract. The short (S) allele was defined as an allele with < 25 dinucleotide repeats in the GT tract.

Based on the results of genetic analysis, participants were genotyped as LL homozygotes, SS homozygotes, or LS heterozygotes. Participants’ concussion recovery time was followed prospectively until the full return to play clearance date determined by the treating physician.

Participant’s recovery time was categorized as normal (≤ 20 days) or prolonged (> 20 days). The DNA region surrounding position (-975 to -776) in the promoter of GRIN2A was amplified by PCR, and was analyzed by capillary electrophoresis. Fragment length polymorphism analysis was performed by measuring the migration time of a PCR product, and extrapolation to the known fragments in the DNA standard ladder using computer software. The number of GT dinucleotide repeats was calculated using the following equation: n(GT)=(L -167)/2, where L is the length of the PCR fragment estimated in base pairs.

Results indicated there was a significant association between the GT VNTR (recessive model: LL versus SS + LS) and recovery, where the chance of prolonged recovery was 4.3 times greater for homozygous carriers of the long allele.

“Making the genetic connection in this data is an exciting step for concussion injury research,” said Dr. McDevitt. “Knowing this information could help improve monitoring and management of athletes who experience concussion, and may also aid in the development of genetic counseling in athletes exposed to concussive head impacts.”