B-cell lymphoma 2 (Bcl-2) gene is associated with intracranial hypertension after severe traumatic brain injury


Deng H, et al. J Neurotrauma 2020.


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) 4-8 and at least 24

hours of ICP monitoring, treated between 2000-2014. Outcomes were mean ICP, spikes >20 and >25 mmHg, edema and surgical intervention. Odds ratios (OR), mean increases/decreases (B), and 95% confidence intervals 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 mmHg for patients with homozygous wild-type (AA), 12.8±0.6 mmHg for heterozygous (AG), and 14.3±1.2 mmHg for homozygous variant (GG) (p =0.023). Rs17759659 GG genotype was associated with more ICP spikes >20 mmHg (p=0.017) and >25 mmHg (p =0.048). Multivariate analysis showed that GG relative to AA genotype had higher ICP (B=+2.7 mmHg, 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.