| Title: |
Aspirin Exposure Reveals Novel Genes Associated with Platelet Function and Cardiovascular Events (outpatient cardiology)
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| Organism(s): |
Homo sapiens
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| Description: |
Background: Identifying individuals at heightened cardiovascular risk is a priority for reducing the global burden of cardiovascular disease. Aspirin is widely used to prevent cardiovascular events, though with variable results. Therefore, we hypothesized that aspirin exposure would reveal novel biological pathways relevant to the development of cardiovascular events. Methods: We administered aspirin, followed by peripheral blood RNA microarray profiling, in a discovery cohort of healthy volunteers (n = 50, HV1), followed by two validation cohorts of healthy volunteers (n = 53, HV2) or outpatient cardiology (OPC, n = 25) patients, in conjunction with platelet function testing with the platelet functions score (PFS, HV1 and HV2) or the VerifyNow Asprin (VN, OPC) test. Sets of coexpressed genes, or “Factors” were identified via Bayesian sparse factor analysis and associated with platelet function in HV1 and validated in HV2 and OPC. Validated factors were associated with death/MI in observational (n = 191) and case:control (n = 447) patient cohorts with available RNA data collected at the time of cardiac catheterization. Results: Factor analysis yielded 20 Factors, of which one, Factor 14, contained 60 genes and was associated with PFS in HV1 (r = -0.31, p-value = 0.03). Factor 14 was associated with platelet function with the same strength and direction in HV2 (r = -0.34, p-value = 0.02) and OPC (one-sided p-value for aspirin resistant vs. aspirin sensitive = 0.046), thus validating the association. Factor 14 was associated with death/MI in the two patient cohorts, odds ratio (OR) = 1.2, 95% CI [1.02-1.4], p-value = 0.01 and hazard ratio = 1.5, [1.2-1.9], p = 0.001, respectively, independent of known cardiovascular risk factors (combined OR = 1.2, CI = [1.02, 1.4], p = 0.03). Factor 14 and the expression of the Factor 14 transcript most highly correlative of PFS, ITGA2B, improved reclassification compared to traditional risk factors (category-free net reclassification index = 31% and 37%, p ? 0.0002 for both). Conclusions: By challenging humans subjects with aspirin, a medication used for cardiovascular risk reduction, we elucidated genes and pathways that may underlie platelet function and mechanisms responsible for cardiovascular death/MI. This accession represents the OPC cohort microarray data 26 subjects selected for microarray analysis were divided into three groups: aspirin resistant (AR, n=8, >550 ARU), high normal (HN, n=9, ARU 500-549) and aspirin sensitive (AS, n=9, ARU<500)
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| Design(s): |
transcription profiling by array
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| Experimental factor(s): |
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| group
3
recorded
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aspirin resistant
aspirin sensitive
high normal
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| Publication(s): |
Fallahi P, Katz R, Toma I, Li R, Reiner J, VanHouten K, Carpio L, Marshall L, Lian Y, Bupp S, Fu SW, Rickles F, Leitenberg D, Lai Y, Weksler BB, Rebling F, Yang Z, McCaffrey TA
Aspirin insensitive thrombophilia: transcript profiling of blood identifies platelet abnormalities and HLA restriction.
PubMed:23454623
Voora D, Cyr D, Lucas J, Chi JT, Dungan J, McCaffrey TA, Katz R, Newby LK, Kraus WE, Becker RC, Ortel TL, Ginsburg GS
Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events.
PubMed:23831034
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| Sample attribute(s): |
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| Material Type
1
recorded
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total RNA
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| AspirinResistanceScore
3
recorded
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>550
<500
500-549
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| AspirinDosage
1
recorded
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81 mg/day
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| Aspirin
1
recorded
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acetylsalicylic acid
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| organism part
1
recorded
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peripheral blood
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| Label
1
recorded
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Biotin
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| TreatmentDuration
1
recorded
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7-10 day
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| group
3
recorded
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aspirin resistant
aspirin sensitive
high normal
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| organism
1
recorded
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Homo sapiens
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| Contact(s): |
Timothy McCaffrey Deepak Voora
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| Release Date: |
12/6/2013
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| Submission Date: |
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| Metadata Downloads |
Download Study Metadata as ISAtabDownload Study Metadata as ISAtab
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| Assay Downloads |
| transcription profiling using DNA microarray
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| 26 assays |
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