title: Gene expression signatures of coronary heart disease.
abstract: OBJECTIVE
  To identify transcriptomic biomarkers of coronary heart disease (CHD) in 188 cases with CHD and 188 age- and sex-matched controls who were participants in the Framingham Heart Study.
  
  
  RESULTS
  A total of 35 genes were differentially expressed in cases with CHD versus controls at false discovery rate<0.5, including GZMB, TMEM56, and GUK1. Cluster analysis revealed 3 gene clusters associated with CHD, 2 linked to increased erythrocyte production and a third to reduced natural killer and T cell activity in cases with CHD. Exon-level results corroborated and extended the gene-level results. Alternative splicing analysis suggested that GUK1 and 38 other genes were differentially spliced in cases with CHD versus controls. Gene Ontology analysis linked ubiquitination and T-cell-related pathways with CHD.
  
  
  CONCLUSIONS
  Two bioinformatically defined groups of genes show consistent associations with CHD. Our findings are consistent with the hypotheses that hematopoesis is upregulated in CHD, possibly reflecting a compensatory mechanism, and that innate immune activity is disrupted in CHD or altered by its treatment. Transcriptomic signatures may be useful in identifying pathways associated with CHD and point toward novel therapeutic targets for its treatment and prevention.
authors.affiliation: The National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
authors.forename: Roby
authors.initials: R
authors.lastname: Joehanes
authors.forename: Saixia
authors.initials: S
authors.lastname: Ying
authors.forename: Tianxiao
authors.initials: T
authors.lastname: Huan
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Johnson
authors.forename: Nalini
authors.initials: N
authors.lastname: Raghavachari
authors.forename: Richard
authors.initials: R
authors.lastname: Wang
authors.forename: Poching
authors.initials: P
authors.lastname: Liu
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Woodhouse
authors.forename: Shurjo K
authors.initials: SK
authors.lastname: Sen
authors.forename: Kahraman
authors.initials: K
authors.lastname: Tanriverdi
authors.forename: Paul
authors.initials: P
authors.lastname: Courchesne
authors.forename: Jane E
authors.initials: JE
authors.lastname: Freedman
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Munson
mesh_terms: D017677:Age Distribution; D000368:Aged; D016022:Case-Control Studies; D016000:Cluster Analysis; D003327:Coronary Disease / Q000453:epidemiology* / Q000235:genetics*; D004274:DNA, Recombinant / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D053804:Granzymes / Q000235:genetics; D006801:Humans; D015994:Incidence; D008297:Male; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008875:Middle Aged; D025581:Neurofibromin 2 / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012016:Reference Values; D015203:Reproducibility of Results; D012307:Risk Factors; D017678:Sex Distribution; D059467:Transcriptome / Q000235:genetics*
chemical_list: D004274:DNA, Recombinant; C490073:MACO1 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D025581:Neurofibromin 2; C509213:GZMB protein, human; D053804:Granzymes
keywords: biomarkers; coronary artery disease; coronary heart disease; gene expression; myocardial infarction; transcriptomics
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