Neuroglobin genetic polymorphisms and their relationship to functional outcomes following traumatic brain injury.

摘要

Background. Neuroglobin (Ngb) is a protein that increases oxygen availability in ischemic neuronal tissues, but whether Ngb gene variants contribute to patient outcomes is unknown.;Purpose. To identify functional or non-functional variants in the Ngb gene in severe traumatic brain injury (TBI) patients and determine whether variants impact patients' injury severity and functional outcomes.;Specific Aims. To identify Ngb variants (present/absent) in DNA extracted from the cerebral spinal fluid and blood of patients with severe TBI, and then: (1) determine the variant frequencies, (2) determine demographic and clinical patient characteristics based on Ngb variants, (3) determine the relationship between the variants and TBI severity as measured by admission Glasgow Coma Scale (GCS), and (4) determine differences in functional outcomes (Glasgow Outcome Scale [GOS]) at 3, 6, 12, and 24 months post TBI based on Ngb variants.;Methods. Prospective, descriptive, comparative design using DNA collected (NIH NR04801 and NS30318) from 196 Caucasian subjects (non-Caucasians excluded to eliminate confounding from ancestry). We generated Ngb genotype data for 2 tagging single nucleotide polymorphism (SNP) variants (captures all of Ngb's genetic variation) using TaqMan PCR technology. Data analysis: independent t-tests; Fisher Exact, Pearson's Chi-square, Exact tests; logistic and linear regression.;Results. For Ngb SNP1, 36.3% were CC/CT (non-wild typed or present variant [SNP1 Vpresent]), and 62.2% were TT (wild typed or absent variant [SNP1 Vabsent]). For Ngb SNP2, only 6.6% were TT/GT (SNP2 Vpresent), whereas 91.3% were GG (SNP2 Vabsent). There was no significant relationship between variants of SNP1 or SNP2 and either demographic or clinical characteristics. There was a trend toward significance between SNP1 Vabsent and better GCS (p = 0.061), but not between SNP2 variants and GCS ( p = 0.109). Subjects with good outcome by GOS were more likely to be SNP1 Vabsent at 3, 6, 12, and 24 months (p = 0.023; p = 0.01; p = 0.002; p = 0.035 respectively). No significant relationship was found between SNP2 and GOS at any time point. Using logistic and linear regression controlling for age, gender, and GCS, SNP1 Vpresent was significantly associated with poorer GOS at 12 months (p = 0.028) only; SNP2 showed no significance in regression analysis.;Conclusion. SNP1 Vabsent TBI patients were more likely to have good outcomes, whereas genetic variants of SNP2 did not impact outcomes; possibly because Ngb SNP1 Vabsent affects the quantity or quality of Ngb in severe TBI, producing better outcomes.