title: Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism.
abstract: BACKGROUND
  Recurrent venous thromboembolism (VTE) occurs infrequently following a provoked event but occurs in up to 30% of individuals following an initial unprovoked event. There is limited understanding of the biological mechanisms that predispose patients to recurrent VTE.
  
  
  OBJECTIVE
  To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE.
  
  
  METHODS
  We studied 107 patients with VTE separated into 3 groups: (1) 'low-risk' patients had one or more provoked VTE; (2) 'moderate-risk' patients had a single unprovoked VTE; (3) 'high-risk' patients had ≥2 unprovoked VTE. Each patient group was also compared to twenty-five individuals with no personal history of VTE. Total RNA from whole blood was isolated and hybridized to Illumina HT-12V4 Beadchips to assay whole genome expression.
  
  
  RESULTS
  Using class prediction analysis, we distinguished high-risk patients from low-risk patients and healthy controls with good receiver operating curve characteristics (AUC=0.81 and 0.84, respectively). We also distinguished moderate-risk individuals and low-risk individuals from healthy controls with AUC's of 0.69 and 0.80, respectively. Using differential expression analysis, we identified several genes previously implicated in thrombotic disorders by genetic analyses, including SELP, KLKB1, ANXA5, and CD46. Protein levels for several of the identified genes were not significantly different between the different groups.
  
  
  CONCLUSIONS
  Gene expression profiles are capable of distinguishing patients with different clinical presentations of VTE, and genes relevant to VTE risk are frequently differentially expressed in these comparisons.
authors: Thrombosis and Hemostasis Center, Division of Hematology, Duke University Medical Center, Durham, NC.
authors: Deborah A
authors: DA
authors: Lewis
authors: Center for Applied Genomics, Duke University School of Medicine, Durham NC.
authors: Sunil
authors: S
authors: Suchindran
authors: Centers for Disease Control and Prevention, Atlanta, GA; Division of Cardiovascular Diseases.
authors: Michele G
authors: MG
authors: Beckman
authors: Centers for Disease Control and Prevention, Atlanta, GA; Division of Cardiovascular Diseases.
authors: W Craig
authors: WC
authors: Hooper
authors: Centers for Disease Control and Prevention, Atlanta, GA; Division of Cardiovascular Diseases.
authors: Althea M
authors: AM
authors: Grant
authors: Mayo Clinic, Rochester, MN.
authors: John A
authors: JA
authors: Heit
authors: University of Colorado and Children's Hospital, Aurora, CO.
authors: Marilyn
authors: M
authors: Manco-Johnson
authors: University of North Carolina, Chapel Hill, NC.
authors: Stephan
authors: S
authors: Moll
authors: Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ.
authors: Claire S
authors: CS
authors: Philipp
authors: Centers for Disease Control and Prevention, Atlanta, GA; Division of Cardiovascular Diseases.
authors: Kristy
authors: K
authors: Kenney
authors: Centers for Disease Control and Prevention, Atlanta, GA; Division of Cardiovascular Diseases.
authors: Christine
authors: C
authors: De Staercke
authors: Centers for Disease Control and Prevention, Atlanta, GA; Division of Cardiovascular Diseases.
authors: Meredith E
authors: ME
authors: Pyle
authors: Department of Molecular Genetics and Microbiology and Center for Genomic and Computation Biology, Duke University Medical Center, Durham NC.
authors: Jen-Tsan
authors: JT
authors: Chi
authors: Thrombosis and Hemostasis Center, Division of Hematology, Duke University Medical Center, Durham, NC. Electronic address: thomas.ortel@duke.edu.
authors: Thomas L
authors: TL
authors: Ortel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D059467:Transcriptome / Q000235:genetics*; D054556:Venous Thromboembolism / Q000097:blood* / Q000188:drug therapy
keywords: deep-vein thrombosis; gene expression profiling; venous thrombosis