Association of p53 Gene Polymorphism with Functional Outcome among Traumatic Brain Injury patients: A Cohort Study

Abstract

Introduction: Traumatic brain injury is one of the leading cause of mortality. The guardian of genome p53 and polymorphism of this gene has been least studied in TBI. Evaluation of the patterns of Arg 72 Pro polymorphism of p53 gene in TBI patients as compared to controls as well as to evaluate the association of p53 gene polymorphisms with the functional outcome of TBI were the objectives of this study.

Methods: The influence of the Arginine variant of p53 was investigated in a cohort of 58 adults with mild, moderate, and severe TBI with PCR-RFLP method.The neuropsychiatric outcomes of the patients were assessed after 3 and 6 months of injury using the following questionnaires; (i) Extended Glasgow Outcome Scale (GOSE)- measure global functioning (ii) Rivermead Head Injury Follow-up Questionnaire (RHFUQ) an index of psychosocial outcome; (iii)Quality of Life after Brain Injury- Overall Scale (QOLIBRI-OS) an index of health-related quality of life after brain injury.

Results: No significant difference was observed between the allelic distribution of genotype variants among cases and controls. The mean value of GCS was highest in patients with CC genotype. The highest GOSE score was observed in proline containing genotype (CC), suggesting a better outcome. Among all the outcome tools used, RFHUQ3 was the most sensitive (85.7%) and specific (90%) with a cut-off value of 6.5. The area under the curve (AUC) was the highest for RFHUQ at 3 months (0.958).

Conclusion: There was no significant association between p53 gene polymorphism and functional outcome after TBI. However, patients with CC genotype (proline/proline) had less severe injuries, whereas the extent of recovery was maximum in GG-containing genotypes, supported by their longest length of hospital stay. RHFUQ was the most sensitive and specific tool to assess the functional outcome after TBI when GOSE is the gold standard.