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Abstract
Objective: Transient ischemic attacks (TIA) are common. Though systemic inflammation and thrombosis are associated with TIA, further study may provide insight into TIA pathophysiology and possibly lead to the development of treatments specifically targeted to TIA. We sought to determine whether gene expression profiles in blood could better characterize the proinflammatory and procoagulant states in TIA patients.
Methods: RNA expression in blood of TIA patients (n = 26) was compared to vascular risk factor control subjects without symptomatic cardiovascular disease (n = 26) using Affymetrix U133 Plus 2.0 microarrays. Differentially expressed genes in TIA were identified by analysis of covariance and evaluated with cross-validation and functional analyses.
Results: Patients with TIA had different patterns of gene expression compared to controls. There were 480 probe sets, corresponding to 449 genes, differentially expressed between TIA and controls (false discovery rate correction for multiple comparisons, p ≤ 0.05, absolute fold change ≥1.2). These genes were associated with systemic inflammation, platelet activation, and prothrombin activation. Hierarchical cluster analysis of the identified genes suggested the presence of 2 patterns of RNA expression in patients with TIA. Prediction analysis identified a set of 34 genes that discriminated TIA from controls with 100% sensitivity and 100% specificity.
Conclusion: Patients with recent TIA have differences of gene expression in blood compared to controls. The 2 gene expression profiles associated with TIA suggests heterogeneous responses between subjects with TIA that may provide insight into cause, risk of stroke, and other TIA pathophysiology.
GLOSSARY
- CRP=
- C-reactive protein;
- FDR=
- false discovery rate;
- LDA=
- linear discriminant analysis;
- TIA=
- transient ischemic attack;
- vWF=
- von Willebrand factor
Footnotes
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Study funding: This study was supported by NIH/NINDS grant NS056302, the AHA Bugher Foundation (F.R.S., B.P.A., H.X., and Y.T.), and NIH/NINDS K02 NS058760 (C.D.B.). Dr. Jickling is a fellow of the Canadian Institutes of Health Research (CIHR). Drs. Xu, Ander, and Tian are AHA Bugher Fellows. Dr. Turner is supported by a National Health and Medical Research Council (Australia) Postdoctoral Fellowship. Dr. Bushnell receives research support from NIH/NINDS K02 NS058760.
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Editorial, page 1716
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Supplemental data at www.neurology.org
- Received February 16, 2011.
- Accepted May 4, 2011.
- Copyright © 2011 by AAN Enterprises, Inc.
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- Gene expression patterns may be confounded by concomitant medications
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