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Mitochondrial DNA and traumatic brain injury.

Mitochondrial DNA and traumatic brain injury.
Mitochondrial DNA and traumatic brain injury.
Objective: 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.

Methods: 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 APOE was applied to Glasgow Outcome Score (GOS) data.

Results: mtDNA had a significant association with 6-month GOS (p?=?0.008). Haplogroup K was significantly associated with favorable outcome (odds ratio?=?1.64, 95% confidence interval?=?1.08–2.51, p?=?0.02). There was also a significant interaction between mitochondrial genome and age (p?=?0.002), with a strong protective effect of both haplogroups T (p?=?0.015) and K (p?=?0.017) with advancing age. We also found a strong interaction between APOE and mitochondrial haplogroups (p?=?0.001), indicating a protective effect of haplogroup K in carriers of the APOE ?4 allele.

Interpretation: 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 APOE 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
0364-5134
186-195
Bulstrode, Harry
7d977124-acda-4e5f-91b5-183105c297f7
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Hudson, Gavin
cbad491d-cc7f-4bea-b214-b6752151fc13
Chinnery, Patrick F
87789d1a-5265-4815-9f11-194ed9b4ad94
Di Pietro, Valentina
52a26fb6-7579-4cdc-aee6-26cb6e9ff175
Belli, Antonio
33707b7b-b004-4245-aead-98a8e1e2b2e2
Bulstrode, Harry
7d977124-acda-4e5f-91b5-183105c297f7
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Hudson, Gavin
cbad491d-cc7f-4bea-b214-b6752151fc13
Chinnery, Patrick F
87789d1a-5265-4815-9f11-194ed9b4ad94
Di Pietro, Valentina
52a26fb6-7579-4cdc-aee6-26cb6e9ff175
Belli, Antonio
33707b7b-b004-4245-aead-98a8e1e2b2e2

Bulstrode, Harry, Nicoll, James A.R., Hudson, Gavin, Chinnery, Patrick F, Di Pietro, Valentina and Belli, Antonio (2014) Mitochondrial DNA and traumatic brain injury. Annals of Neurology, 75 (2), 186-195. (doi:10.1002/ana.24116). (PMID:24523223)

Record type: Article

Abstract

Objective: 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.

Methods: 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 APOE was applied to Glasgow Outcome Score (GOS) data.

Results: mtDNA had a significant association with 6-month GOS (p?=?0.008). Haplogroup K was significantly associated with favorable outcome (odds ratio?=?1.64, 95% confidence interval?=?1.08–2.51, p?=?0.02). There was also a significant interaction between mitochondrial genome and age (p?=?0.002), with a strong protective effect of both haplogroups T (p?=?0.015) and K (p?=?0.017) with advancing age. We also found a strong interaction between APOE and mitochondrial haplogroups (p?=?0.001), indicating a protective effect of haplogroup K in carriers of the APOE ?4 allele.

Interpretation: 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 APOE 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

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Accepted/In Press date: 4 February 2014
Published date: February 2014
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 394802
URI: https://eprints.soton.ac.uk/id/eprint/394802
ISSN: 0364-5134
PURE UUID: f6dfa346-24ad-4fc0-8fd2-7cde565d7e9a
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

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Date deposited: 24 May 2016 10:36
Last modified: 31 Jul 2019 00:45

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