Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Lewis, Deborah A.; Suchindran, Sunil; Beckman, Michele G.; Hooper, W. Craig; Grant, Althea M.; Heit, John A.; Manco-Johnson, Marilyn; Moll, Stephan; Philipp, Claire S.; Kenney, Kristy; De Staercke, Christine; Pyle, Meredith E.; Chi, Jen-Tsan; Ortel, Thomas L.
• Is Part Of: Thrombosis research. Volume 135:Issue 4(2015)
• Page Start: 659
• Page End: 665
• Publication Date: 2015-04
• Subjects: Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2015.02.003
• Languages: English
• ISSNs: 0049-3848

Abstract

<abstract abstract-type="author" id="ab0005"> <title id="st0005">Abstract</title> <sec> <title id="st0010">Introduction</title> <p id="sp0005">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.</p> </sec> <sec> <title id="st0015">Objectives</title> <p id="sp0010">To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE.</p> </sec> <sec> <title id="st0070">Patients/Methods</title> <p id="sp0015">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-12 V4 Beadchips to assay whole genome expression.</p> </sec> <sec> <title id="st0020">Results</title> <p id="sp0020">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 <italic>SELP</italic>, <italic>KLKB1</italic>, <italic>ANXA5</italic>, and <italic>CD46</italic>. Protein levels for several of the identified genes were not significantly different between the different groups.</p> </sec> <sec> <title id="st0025">Conclusion</title> <p id="sp0025">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.</p> </sec> </abstract>