Association between (GT)n Promoter Polymorphism and Recovery from Concussion: A Pilot Study

• Published in: Journal of neurotrauma Vol. 37; no. 10; pp. 1204 - 1210
• Main Authors: McDevitt, Jane, Rubin, Leah H, De Simone, Francesca I, Phillips, Jaqueline, Langford, Dianne
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 15.05.2020
• Subjects: Alleles; Athletes; Capillary electrophoresis; Concussion; Deoxyribonucleic acid; DNA; Gene polymorphism; Genes; Genetic diversity; Genomes; Glutamic acid receptors (ionotropic); N-Methyl-D-aspartic acid receptors; Polymorphism; Potassium; Potassium channels (voltage-gated); Proteins; Recovery (Medical); Regression analysis; Risk factors; Sports injuries; repeat polymorphism; NEFL gene; VNTR; GRIN2A gene
• ISSN: 0897-7151; 1557-9042
• DOI: 10.1089/neu.2019.6590

Variability in recovery among concussed athletes can be attributed to several risk factors. One risk factor not definitively explored is genetic variation. Genetic variations such as variable number tandem repeats (VNTR) in the promotor region are normal in the population, and can lead to disparities in the amount of protein produced, which could be associated with neuronal recovery. Little research has been conducted to investigate promoter VNTRs within genes responsible for recovery following a concussion. The authors implemented a prospective cohort design using a standardized concussion protocol to diagnose and follow 93 athletes to full recovery at three different sites to determine the association between promotor GT(n) VNTR polymorphisms and recovery time within concussed athletes. The GT(n) VNTR within the promoter region of glutamate ionotropic receptor methyl-d-aspartate (NMDA) type subunit 2A ( ), potassium voltage-gated channel subfamily H member 2 ( ), glutamate ionotropic receptor kainate type subunit 1 ( ), and neurofilament light ( ) were genotyped using capillary electrophoresis. GT(n) VNTR promotor polymorphisms were dichotomized into long (L) and short (s) alleles. Using adjusted negative binomial regression models we found that athletes carrying the LL GT(n) VNTR within the promoter region were more likely to experience a prolonged concussion recovery, which resulted in their not being able to return to play for ∼60 days. Additionally, there was a trend toward significance, in which the ss GT(n) Caucasian athletes had prolonged concussion recovery. This could presumably be attributed to altered proteins or protein levels that disrupt neuronal recovery. This pilot study suggests that these VNTRs are associated with prolonged concussion recovery. In future studies, we plan to measure the extent to which the L or s alleles alter the level and the activity of the GluNR2a and NEFL proteins that and produce, respectively.