Neuroglobin Genetic Polymorphisms and Their Relationship to Functional Outcomes after Traumatic Brain Injury

Abstract

Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI). However, to date an association between genetic variation within the human neuroglobin (NGB) gene and recovery post-TBI has not been reported. The purpose of this study was to explore the relationship between NGB genotypes and outcomes (as assessed by the Glasgow Outcome Scale [GOS], the Disability Rating Scale [DRS], and the Neurobehavioral Rating Scale-Revised [NRS-R]) after severe TBI. Genotyping using TaqMan allele discrimination for two tagging single nucleotide polymorphisms (tSNPs) that represent the two haplotype blocks for NGB (rs3783988 and rs10133981) was completed on DNA obtained from 196 Caucasian patients recovering from severe TBI. Patients were dichotomized based on the presence of the variant allele for each tSNP. Chi-square and Fisher's exact tests were used to compare characteristics between groups. Multivariate linear regression was used to examine NGB tSNPs and recovery from severe TBI. Subjects with the TT genotype (wild-type) for rs3783988 were more likely to have better GOS and DRS scores at 3, 6, 12, and 24 months, while rs10133981 genotype was not significantly related to functional outcome. After controlling for age, gender, and Glasgow Coma Scale (GCS) score, those subjects with the rs3783988 TT genotype had more than a 2.65-times greater likelihood of better functional outcomes than individuals with genotypes harboring a variant allele. Data suggest that the haplotype block represented by rs3783988 in NGB appears to influence recovery after severe TBI. Represented within this haplotype block of NGB is the region that codes for the oxygen-binding portion of NGB.

Transgenic overexpression of neuroglobin attenuates formation of smoke-inhalation-induced oxidative DNA damage, in vivo, in the mouse brain

“…Importantly, a new clinical study revealed that a two nucleotide polymorphism in the Ngb gene correlates with worse outcomes of traumatic brain injury (TBI) in a cohort of 196 patients [54], which might be associated with a decreased capacity for sustenance of energy metabolism after TBI in surviving patients. Thus, we expect that availability of our new transgenic mouse with neuron-targeted overexpression of neuroglobin, will advance the ability to dissect and potentially constrain molecular mechanisms by which acute exposure to smoke promotes the development of neuronal injury.…”

Neuroglobin overexpression improves sensorimotor outcomes in a mouse model of traumatic brain injury

“…Furthermore, overexpression of neuroglobin in Wistar rats significantly reduced neuron necrosis and apoptosis after TBI in comparison to controls [22]. In humans, genetic polymorphisms in neuroglobin have been shown to positively influence recovery in TBI patients [6]. The present study was designed to determine whether NGB mice displayed improved sensorimotor recovery after TBI in comparison to WT mice.…”

Neuroglobin, a Factor Playing for Nerve Cell Survival

“…Further evidence comes from human population studies, that have associated genetic polymorphisms within the human neuroglobin gene with neuroprotection, while decreased expression of neuroglobin in older people, in women, or associated with single nucleotide polymorphism has been linked to increased risk of Alzheimer’s disease [55,56,57]. …”