4.7 Article

Transient ischemic attacks characterized by RNA profiles in blood

Journal

NEUROLOGY
Volume 77, Issue 19, Pages 1718-1724

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e318236eee6

Keywords

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Funding

  1. National Health and Medical Research Council (Australia)
  2. American Heart Association Bugher Foundation
  3. American Heart Association
  4. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership
  5. NIH/NINDS [NS056302, K02 NS058760]
  6. American Heart Association/Bugher Foundation
  7. Hazel K Goddess Fund for Research on Stroke in Women
  8. sanofi-aventis
  9. Strkyer Neurovascular
  10. Boston Scientific
  11. NIH (NCRR, NINDS)
  12. Kaiser-Permanente
  13. AHA/ASA
  14. AHA Bugher Foundation

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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. Neurology (R) 2011; 77: 1718-1724

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