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: ANXA2 annexin A2 -- ANXA5 annexin A5 -- AUC area under the curve -- C1QB complement component 1, q subcomponent, B chain -- C5 complement component 5 -- CD46 complement regulatory protein -- CDC Centers for Disease Control and Prevention -- CFH complement factor H -- CR1 complement component receptor 1 -- CR2 complement component receptor 2 -- DVT Deep vein thrombosis -- EDN1 endothelin 1 -- F2RL1 coagulation factor II receptor-like 1 -- F11 coagulation factor XI -- HIF1A hypoxia inducible factor 1, alpha subunit -- ICAM-1 intercellular adhesion molecule 1 -- IGF1R insulin-like growth factor 1 receptor -- IL4 interleukin 4 -- ITGAL integrin alpha L chain -- KEGG Kyoto Encyclopedia of Genes and Genomes -- KLKB1 kallikrein B -- PE pulmonary embolism -- PPARD peroxisome proliferator-activated receptor delta -- SELP selectin P -- SERPING1 Serpin peptidase inhibitor Glade G (C1 inhibitor) -- SNPs single nucleotide polymorphisms -- TF transferrin -- VTE venous thromboembolism; venous thrombosis -- deep-vein thrombosis -- gene expression profiling; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2015.02.003
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Introduction: 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. Objectives: To identify whole blood gene expression profiles that distinguished patients with clinically distinct patterns of VTE. Patients/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-12 V4 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. Conclusion: 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. Highlights: Gene expression was used to study 3 groups with VTE and healthy controls. Recurrent unprovoked VTE patients were distinguished from those with provoked VTE. Patients with recurrent unprovoked VTE were also distinguished from controls. Genes specific to coagulation, and immune response were differentially expressed. Seven genes involved in complement activation were also differentially expressed.