title: Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction.
abstract: BACKGROUND
  Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated blood gene expression signature of respiratory viral infection (viral GES) was associated with MI and 2) respiratory viral exposure changes levels of a validated platelet gene expression signature (platelet GES) of platelet function in response to aspirin that is associated with MI.
  
  
  METHODS
  A previously defined viral GES was projected into blood RNA data from 594 patients undergoing elective cardiac catheterization and used to classify patients as having evidence of viral infection or not and tested for association with acute MI using logistic regression. A previously defined platelet GES was projected into blood RNA data from 81 healthy subjects before and after exposure to four respiratory viruses: Respiratory Syncytial Virus (RSV) (n=20), Human Rhinovirus (HRV) (n=20), Influenza A virus subtype H1N1 (H1N1) (n=24), Influenza A Virus subtype H3N2 (H3N2) (n=17). We tested for the change in platelet GES with viral exposure using linear mixed-effects regression and by symptom status.
  
  
  RESULTS
  In the catheterization cohort, 32 patients had evidence of viral infection based upon the viral GES, of which 25% (8/32) had MI versus 12.2% (69/567) among those without evidence of viral infection (OR 2.3; CI [1.03-5.5], p=0.04). In the infection cohorts, only H1N1 exposure increased platelet GES over time (time course p-value = 1e-04).
  
  
  CONCLUSIONS
  A viral GES of non-specific, respiratory viral infection was associated with acute MI; 18% of the top 49 genes in the viral GES are involved with hemostasis and/or platelet aggregation. Separately, H1N1 exposure, but not exposure to other respiratory viruses, increased a platelet GES previously shown to be associated with MI. Together, these results highlight specific genes and pathways that link viral infection, platelet activation, and MI especially in the case of H1N1 influenza infection.
authors.affiliation: Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Rose
authors.affiliation: Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Deepak
authors.initials: D
authors.lastname: Voora
authors.affiliation: Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Derek D
authors.initials: DD
authors.lastname: Cyr
authors.affiliation: Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Lucas
authors.affiliation: Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Aimee K
authors.initials: AK
authors.lastname: Zaas
authors.affiliation: Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Woods
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Center for Applied Genomics and Precision Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ginsburg
mesh_terms: D000368:Aged; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006328:Cardiac Catheterization; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D007251:Influenza, Human / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics* / Q000628:therapy; D010597:Pharmacogenetics; D010850:Picornaviridae Infections / Q000150:complications / Q000235:genetics*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000235:genetics*; D012136:Respiratory Syncytial Viruses; D012229:Rhinovirus; D059467:Transcriptome
chemical_list: D001241:Aspirin