Oxidative phosphorylation and lacunar stroke

Traylor, Matthew, Anderson, Christopher D., Hurford, Robert, 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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