1 School of Nursing, University of Pittsburgh , Pittsburgh, Pennsylvania.
J Neurotrauma. 2014 Jan 1;31(1):34-41. doi: 10.1089/neu.2013.2855. Epub 2013 Nov 14.
Patient outcomes are variable following severe traumatic brain injury (TBI); however, the biological underpinnings explaining this variability are unclear. Mitochondrial dysfunction after TBI is well documented, particularly in animal studies. The aim of this study was to investigate the role of mitochondrial polymorphisms on mitochondrial function and patient outcomes out to 1 year after a severe TBI in a human adult population. The Human MitoChip V2.0 was used to evaluate mitochondrial variants in an initial set of n=136 subjects. SNPs found to be significantly associated with patient outcomes [Glasgow Outcome Scale (GOS), Neurobehavioral Rating Scale (NRS), Disability Rating Scale (DRS), in-hospital mortality, and hospital length of stay] or neurochemical level (lactate:pyruvate ratio from cerebrospinal fluid) were further evaluated in an expanded sample of n=336 subjects. A10398G was associated with DRS at 6 and 12 months (p=0.02) and a significant time by SNP interaction for DRS was found (p=0.0013). The A10398 allele was associated with greater disability over time. There was a T195C by sex interaction for GOS (p=0.03) with the T195 allele associated with poorer outcomes in females. This is consistent with our findings that the T195 allele was associated with mitochondrial dysfunction (p=0.01), but only in females. This is the first study associating mitochondrial DNA variation with both mitochondrial function and neurobehavioral outcomes after TBI in humans. Our findings indicate that mitochondrial DNA variation may impact patient outcomes after a TBI potentially by influencing mitochondrial function, and that sex of the patient may be important in evaluating these associations in future studies.
患者在经历严重创伤性脑损伤（TBI）后的结果存在差异；然而，解释这种差异的生物学基础尚不清楚。TBI 后线粒体功能障碍已有充分的文献记载，尤其是在动物研究中。本研究旨在调查线粒体多态性对人类成年人群重度 TBI 后 1 年内线粒体功能和患者结果的影响。使用 Human MitoChip V2.0 评估了初始 n=136 例受试者中的线粒体变体。发现与患者结果[格拉斯哥结局量表（GOS）、神经行为评定量表（NRS）、残疾评定量表（DRS）、院内死亡率和住院时间]或神经化学水平（脑脊液中乳酸：丙酮酸比值）显著相关的 SNPs 进一步在 n=336 例扩展样本中进行了评估。A10398G 与 6 个月和 12 个月时的 DRS 相关（p=0.02），并且发现 DRS 的 SNP 交互作用具有显著的时间依赖性（p=0.0013）。A10398 等位基因与随时间推移的残疾程度增加相关。GOS 存在 T195C 与性别交互作用（p=0.03），T195 等位基因与女性的较差结局相关。这与我们的发现一致，即 T195 等位基因与线粒体功能障碍相关（p=0.01），但仅在女性中。这是第一项将线粒体 DNA 变异与 TBI 后线粒体功能和神经行为结果相关联的研究。我们的研究结果表明，线粒体 DNA 变异可能通过影响线粒体功能对 TBI 后的患者结果产生影响，并且患者的性别可能在未来的研究中评估这些关联中很重要。
