Analysis of the Genetic Expression of Inflammatory Mediators From Patients with Spontaneous Deep Venous Thrombosis

Abstract 5251

Deep venous thrombosis (DVT) is a multifactorial disease and in about 30% of patients no risk factor can be identified. Association of inflammation and hemostasis is thought to play a significant role in the pathogenesis of DVT. We hypothesized that distinctive patterns of expression of inflammatory mediators in mononuclear cells from patients with previous DVT could be relevant to the pathogenesis of DVT. cDNA microarray technology (CodeLink Bioarrays) was chosen to study the gene expression profile of inflammatory mediators in DVT patients with clinical characteristics of a high penetrance of any putative hereditary risk, and their healthy siblings. These microarrays were hybridized with synthesized probes from pooled samples collected from patients and control siblings. Patients were divided into two clinical groups: (1) patients with one spontaneous DVT (n=2), and (2) patients with recurrent spontaneous DVT episodes (n=1). Preliminary analysis showed that 2% of approximately 55,000 transcripts contained in the array had significant (higher than 2-fold) differences in expression in spontaneous and recurrent spontaneous DVT relative to their asymptomatic siblings. In group 1, 738 genes were upregulated and 504 genes were downregulated. In group 2, 1229 genes were upregulated and 87 genes were downregulated. Genes with different expression compared to controls were associated to immune and inflammatory response, motility, cell adhesion, cell-cell signaling, defense response, signal transduction and apoptosis. Genes that presented the highest differences compared to controls were interleukin 8 (43-fold increase), chemokine (C-X-C motif) ligand 2 (11-fold increase), major histocompatibility complex, class II, DR beta 5 (8-fold increase), major histocompatibility complex, class II, DQ alpha 1 (29-fold decrease), caspase recruitment domain family, member 15 (7-fold increase), carboxypeptidase A5 (11-fold decrease), cathepsin G (8-fold decrease), and azurocidin 1 (3-fold decrease). A comprehensive list of these genes was generated. Evaluation of the significance of these distinctive gene expression profiles between patients with spontaneous and recurrent DVT compared to their asymptomatic siblings could reveal novel insights into the pathophysiology of the first DVT episode and of DVT recurrence, as well as new biomarkers or therapeutic targets.