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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27839 Neurology-2016-Traylor-141-5.pdf - Whole Document Available under License Creative Commons Attribution 4.0 International. 365kB |
Item Type: | Article |
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Item Status: | Live Archive |
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 |
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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 |
Related URLs: | |
ID Code: | 27839 |
Deposited On: | 13 Jul 2017 12:44 |
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