B-Cell Lymphoma 2 (Bcl-2) Gene Is Associated with Intracranial Hypertension after Severe Traumatic Brain Injury.

Abstract

Severe traumatic brain injury (TBI) activates the apoptotic cascade in neurons and glia as part of secondary cellular injury. B-cell lymphoma 2 (Bcl-2) gene encodes a pro-survival protein to suppress programmed cell death, and variation in this gene has potential to affect intracranial pressure (ICP). Participants were recruited from a single clinical center using a prospective observational study design. Inclusion criteria were: age 16-80 years; Glasgow Coma Scale (GCS) score 4-8; and at least 24 h of ICP monitoring treated between 2000-2014. Outcomes were mean ICP, spikes >20 and >25 mm Hg, edema, and surgical intervention. Odds ratios (OR), mean increases/decreases (B), and 95% confidence intervals (CIs) were reported. In 264 patients, average age was 39.2 years old and 78% of patients were male. Mean ICPs were 11.4 ± 0.4 mm Hg for patients with homozygous wild-type (AA), 12.8 ± 0.6 mm Hg for heterozygous (AG), and 14.3 ± 1.2 mm Hg for homozygous variant (GG; p = 0.023). Rs17759659 GG genotype was associated with more ICP spikes >20 mm Hg (p = 0.017) and >25 mm Hg (p = 0.048). Multi-variate analysis showed that GG relative to AA genotype had higher ICP (B = 2.7 mm Hg, 95% CI [0.5,4.9], p = 0.015), edema (OR = 2.5 [1.0, 6.0], p = 0.049) and need for decompression (OR = 3.7 [1.5-9.3], p = 0.004). In this prospective severe TBI cohort, Bcl-2 rs17759659 was associated with increased risk of intracranial hypertension, cerebral edema, and need for surgical intervention. The variant allele may impact programmed cell death of injured neurons, resulting in elevated ICP and post-traumatic secondary insults. Further risk stratification and targeted genotype-based therapies could improve outcomes after severe TBI.