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Mitochondrial polymorphisms impact outcomes after severe traumatic brain injury
Yvette P Conley1, David O Okonkwo, Sandra Deslouches
11 School of Nursing, University of Pittsburgh , Pittsburgh, Pennsylvania.
Journal of Neurotrauma
|July 26, 2013
Summary
Mitochondrial DNA variations influence outcomes after severe traumatic brain injury (TBI). Specific genetic variants are linked to increased disability and poorer neurobehavioral outcomes, highlighting their role in TBI patient variability.
Area of Science:
- Neuroscience
- Genetics
- Mitochondrial Biology
Background:
- Patient outcomes after severe traumatic brain injury (TBI) exhibit significant variability.
- The biological basis for this outcome variability remains largely unexplained.
- Mitochondrial dysfunction is a known consequence of TBI, particularly observed in animal models.
Purpose of the Study:
- To investigate the impact of mitochondrial DNA (mtDNA) polymorphisms on mitochondrial function.
- To determine the association between mtDNA variants and patient outcomes up to one year post-severe TBI in humans.
- To explore potential sex-specific effects of mtDNA variation on TBI outcomes.
Main Methods:
- Mitochondrial variants were assessed using the Human MitoChip V2.0 in an initial cohort of 136 subjects.
- Single Nucleotide Polymorphisms (SNPs) significantly associated with outcomes or neurochemical levels were further analyzed in an expanded cohort of 336 subjects.
- Patient outcomes were measured using the Glasgow Outcome Scale (GOS), Neurobehavioral Rating Scale (NRS), and Disability Rating Scale (DRS), alongside in-hospital mortality and hospital length of stay.
Main Results:
- The A10398G polymorphism was associated with increased disability over time, as measured by the Disability Rating Scale (DRS) at 6 and 12 months (p=0.02).
- A significant time by SNP interaction for DRS was observed (p=0.0013).
- A T195C polymorphism showed a sex interaction for GOS (p=0.03), with the T195 allele linked to poorer outcomes in females, correlating with impaired mitochondrial function in this group (p=0.01).
Conclusions:
- Mitochondrial DNA variation may influence patient outcomes following severe TBI, potentially through effects on mitochondrial function.
- Specific mtDNA variants, such as A10398G and T195C, are associated with neurobehavioral outcomes and disability.
- Patient sex is a crucial factor to consider in future studies investigating the relationship between mtDNA variation and TBI outcomes.
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