Oxidative phosphorylation and lacunar stroke

Traylor, Matthew and Anderson, Christopher D. and Hurford, Robert and Bevan, Steve and Markus, Hugh S. (2016) Oxidative phosphorylation and lacunar stroke. Neurology, 86 (2). pp. 141-145. ISSN 0028-3878

Full content URL: http://dx.doi.org/10.1212/WNL.0000000000002260

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Abstract

OBJECTIVE:

We investigated whether oxidative phosphorylation (OXPHOS) abnormalities were associated with lacunar stroke, hypothesizing that these would be more strongly associated in patients with multiple lacunar infarcts and leukoaraiosis (LA).
METHODS:

In 1,012 MRI-confirmed lacunar stroke cases and 964 age-matched controls recruited from general practice surgeries, we investigated associations between common genetic variants within the OXPHOS pathway and lacunar stroke using a permutation-based enrichment approach. Cases were phenotyped using MRI into those with multiple infarcts or LA (MLI/LA) and those with isolated lacunar infarcts (ILI) based on the number of subcortical infarcts and degree of LA, using the Fazekas grading. Using gene-level association statistics, we tested for enrichment of genes in the OXPHOS pathway with all lacunar stroke and the 2 subtypes.
RESULTS:

There was a specific association with strong evidence of enrichment in the top 1% of genes in the MLI/LA (subtype p = 0.0017) but not in the ILI subtype (p = 1). Genes in the top percentile for the all lacunar stroke analysis were not significantly enriched (p = 0.07).
CONCLUSIONS:

Our results implicate the OXPHOS pathway in the pathogenesis of lacunar stroke, and show the association is specific to patients with the MLI/LA subtype. They show that MRI-based subtyping of lacunar stroke can provide insights into disease pathophysiology, and imply that different radiologic subtypes of lacunar stroke subtypes have distinct underlying pathophysiologic processes.

Keywords:Stroke, NotOAChecked
Subjects:C Biological Sciences > C400 Genetics
C Biological Sciences > C420 Human Genetics
C Biological Sciences > C440 Molecular Genetics
C Biological Sciences > C431 Medical Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:27839
Deposited On:13 Jul 2017 12:44

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