Genetic Variation in the TP53 Gene and Patient Outcomes Following Severe Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability, with more than 5 million people in the United States living with long-term complications related to TBI. This study examined the relationship between TP53, the gene that codes for the protein p53, and outcome variability following severe TBI. The p53 protein impacts neuronal apoptosis following TBI, thus investigation into TP53 genetic variability as a prognosticator for TBI outcomes (mortality, Glasgow Outcome Scale [GOS], Neurobehavioral Rating Scale [NRS], and Disability Rating Scale [DRS]) is warranted. Participants (N = 429) with severe TBI (Glasgow Coma Scale score ≤8) were enrolled into a prospective study with outcomes assessed over 24 months following injury. The single-nucleotide polymorphism Arg72Pro (rs1042522), a functional missense polymorphism for which the CC homozygous genotype is most efficient at inducing apoptosis, was investigated. Individuals with the CC genotype (arginine homozygotes) were more likely to have poorer outcomes at 24 months following TBI compared to individuals with CG/GG genotypes (GOS: p = .048, DRS: p = .022). These findings add to preliminary evidence that p53 plays a role in recovery following TBI and, if further replicated, could support investigations into p53-based therapies for treating TBI.