Mitochondrial DNA and traumatic brain injury. Issue 2 (1st March 2014)

• Record Type: Journal Article
• Authors: Bulstrode, Harry; Nicoll, James A. R.; Hudson, Gavin; Chinnery, Patrick F.; Di Pietro, Valentina; Belli, Antonio
• Is Part Of: Annals of neurology. Volume 75:Issue 2(2014:Feb.)
• Page Start: 186
• Page End: 195
• Publication Date: 2014-03-01
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.24116
• Languages: English
• ISSNs: 0364-5134

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ana24116-sec-0001" sec-type="section"> <title>Objective</title> <p>Traumatic brain injury (TBI) is a multifactorial pathology with great interindividual variability in response to injury and outcome. Mitochondria contain their own DNA (mtDNA) with genomic variants that have different physiological and pathological characteristics, including susceptibility to neurodegeneration. Given the central role of mitochondria in the pathophysiology of neurological injury, we hypothesized that its genomic variants may account for the variability in outcome following TBI.</p> </sec> <sec id="ana24116-sec-0002" sec-type="section"> <title>Methods</title> <p>We undertook an analysis of mitochondrial haplogroups in a large, well‐characterized cohort of 1, 094 TBI patients. A proportional odds model including age, brain computed tomography characteristics, injury severity, pupillary reactivity, mitochondrial haplogroups, and <italic>APOE</italic> was applied to Glasgow Outcome Score (GOS) data.</p> </sec> <sec id="ana24116-sec-0003" sec-type="section"> <title>Results</title> <p>mtDNA had a significant association with 6‐month GOS (<italic>p</italic> = 0.008). Haplogroup K was significantly associated with favorable outcome (odds ratio = 1.64, 95% confidence interval = 1.08–2.51, <italic>p</italic> = 0.02). There was also a significant interaction between mitochondrial genome and age (<italic>p</italic> = 0.002), with a strong protective effect of both haplogroups T (<italic>p</italic> = 0.015) and K (<italic>p</italic> = 0.017) with advancing age. We also found a strong interaction between <italic>APOE</italic> and mitochondrial haplogroups (<italic>p</italic> = 0.001), indicating a protective effect of haplogroup K in carriers of the <italic>APOE</italic> ε4 allele.</p> </sec> <sec id="ana24116-sec-0004" sec-type="section"> <title>Interpretation</title> <p>These findings reveal an interplay between mitochondrial DNA, pathophysiology of TBI, and aging. Haplogroups K and T, which share a common maternal ancestor, are shown as protective in TBI. The data also suggest that the <italic>APOE</italic> pathways interact with genetically regulated mitochondrial functions in the response to acute injury, as previously reported in Alzheimer disease. Ann Neurol 2014;75:186–195</p> </sec> </abstract>