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Doctoral thesis
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A network-based approach to elucidate determinants of platelet reactivity in aspirin-treated cardiovascular patients

Defense date2012-12-19
Abstract

High residual platelet reactivity (PR) in aspirin-treated cardiovascular patients (CV) is at risk for ischemic events. The determinants of this phenotype are unknown but suggested to be genetically determined. PR was assessed in 110 CV patients treated with aspirin 100mg/day. CV patients with extreme high or low PR were selected for ‘omic analysis, characterizing about 1000 platelet proteins and 6000 transcripts differentially expressed. A genome-wide association study of single nucleotide polymorphisms allowed mapping genetic variants between extreme patients. These datasets were integrated using a network biology approach. The total network was 2077 nodes and 722380 edges. We filtered it by selecting correlations observed at least twice among the different datasets. This resulted in a network with 99 nodes and 309 edges. Preliminary analysis showed a significant enrichment of genes involved in platelet activation, cytoskeleton and glucose metabolism. This may delineate new targets for the prevention of ischemic events in CV patients.

eng
Keywords
  • Platelet reactivity
  • aspirin
  • atherothrombosis
  • network biology
  • proteomics
  • transcriptomics
  • SNP
  • platelet
Citation (ISO format)
ZUFFEREY BAKOS, Anne. A network-based approach to elucidate determinants of platelet reactivity in aspirin-treated cardiovascular patients. 2012. doi: 10.13097/archive-ouverte/unige:29011
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