Aspirin Exposure Reveals Novel Genes Associated with Platelet Function and Cardiovascular Events

Details

• Alternative Title:
  J Am Coll Cardiol
• Personal Author:
  Voora, Deepak ; Cyr, Derek ; Lucas, Joseph ; Chi, Jen-Tsan ; Dungan, Jennifer ; McCaffrey, Timothy A. ; Katz, Richard ; Newby, L. Kristin ; Kraus, William E ; Becker, Richard C. ; Ortel, Thomas L. ; Ginsburg, Geoffrey S.
• Description:
  Objectives
  
  To develop RNA profiles that could serve as novel biomarkers for the response to aspirin.
  
  Background
  
  Aspirin reduces death and myocardial infarction (MI) suggesting that aspirin interacts with biological pathways that may underlie these events.
  
  Methods
  
  We administered aspirin, followed by whole blood RNA microarray profiling, in a discovery cohort of healthy volunteers (HV1,n=50), and two validation cohorts of volunteers (HV2,n=53) or outpatient cardiology patients (OPC, n=25). Platelet function was assessed by platelet function score (PFS; HV1/HV2) or VerifyNow Aspirin (OPC). Bayesian sparse factor analysis identified sets of coexpressed transcripts, which were examined for association with PFS in HV1 and validated in HV2 and OPC. Proteomic analysis confirmed the association of validated transcripts in platelet proteins. Validated gene sets were tested for association with death/MI in two patient cohorts (n=587, total) from RNA samples collected at cardiac catheterization.
  
  Results
  
  A set of 60 co-expressed genes named the “aspirin response signature” (ARS) was associated with PFS in HV1 (r = −0.31, p = 0.03), HV2 (r = −0.34, Bonferroni p = 0.03), and OPC (p = 0.046). Corresponding proteins for 17 ARS genes were identified in the platelet proteome, of which, six were associated with PFS. The ARS was associated with death/MI in both patient cohorts (odds ratio = 1.2, p = 0.01 and hazard ratio = 1.5, p = 0.001), independent of cardiovascular risk factors. Compared with traditional risk factors, reclassification (net reclassification index = 31 - 37%, p ≤ 0.0002) was improved by including the ARS or one of its genes, ITGA2B.
  
  Conclusions
  
  RNA profiles of platelet-specific genes are novel biomarkers for identifying those do not response adequately to aspirin and who are at risk for death/MI.
  
  
• Subjects:
  Article Aspirin Bayes Theorem Biomarkers Blood Platelets Cardiovascular Diseases Genes Humans Microarray Analysis Myocardial Infarction Platelet Aggregation Inhibitors Platelet Function Tests Platelets Proteomics Real-Time Polymerase Chain Reaction Risk Factors RNA

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• Source:
  J Am Coll Cardiol. 2013; 62(14):1267-1276.
• Pubmed ID:
  23831034
• Pubmed Central ID:
  PMC3786046
• Document Type:
  Journal Article
• Funding:
  5RC1GM091083/GM/NIGMS NIH HHS/United States ; 5T32HL007101/HL/NHLBI NIH HHS/United States ; 5U01DD000014/DD/NCBDD CDC HHS/United States ; 5UL1RR024128/RR/NCRR NIH HHS/United States ; KL2 RR024127/RR/NCRR NIH HHS/United States ; RC1 GM091083/GM/NIGMS NIH HHS/United States ; T32 HL007101/HL/NHLBI NIH HHS/United States
• Volume:
  62
• Issue:
  14
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:8c596ee9be24525093c9c21ba39c51b073eb193b996993916738795cda26218d
• Download URL:
  https://stacks.cdc.gov/view/cdc/29750/cdc_29750_DS1.pdf
• File Type:
  [PDF - 847.21 KB ]