title: Toll-like receptor 9 gene expression in the post-thrombotic syndrome, residual thrombosis and recurrent deep venous thrombosis: A case-control study.
abstract: OBJECTIVE
  Animal models suggest that toll-like receptor 9 (TLR9) promotes thrombus resolution after acute deep venous thrombosis (DVT). We hypothesized that TLR9 expression is lower in patients with post-thrombotic syndrome (PTS) and investigated the role of TLR9 in residual thrombosis (RT) and recurrence.
  
  
  METHODS
  Patients with a history of DVT with PTS (cases, n=30) and without PTS after minimal 24 months follow-up (controls, n=30) were selected. Healthy individuals (HI, n=29) without DVT were included as reference. TLR9 mRNA expression in leukocytes was determined by qPCR and normalized to the housekeeping succinate dehydrogenase subunit A gene using the ΔCt method. Sub analyses were performed to explore the TLR9 expression in patients with and without RT and multiple DVT episodes.
  
  
  RESULTS
  The median TLR9 expression was 0.45 (interquartile range 0.31 to 0.93), 0.39 (0.25 to 0.69) and 0.62 (0.32 to 0.75) in cases, controls and HI respectively (p=0.61). The median TLR9 expression was 0.39 (0.26 to 0.51) in patients with RT compared to 0.55 (0.30 to 0.86, p=0.13) in those without. The median TLR9 expression was significantly lower in patients who had one DVT compared to patients with recurrent DVT, 0.37 (0.23 to 0.63) versus 0.55 (0.43 to 0.96) respectively (p<0.01).
  
  
  CONCLUSIONS
  No significant difference in TLR9 expression was found between cases, controls and HI. However TLR9 expression seems lower in individuals with DVT and RT, albeit not significant. Interestingly, TLR9 might play a role in recurrent DVT, as the TLR9 expression was significantly higher in patients with recurrent DVT.
authors.affiliation: Department of Internal Medicine, Flevohospital, Hospitaalweg 1, Almere, The Netherlands; Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands. Electronic address: y.w.cheung@amc.uva.nl.
authors.forename: Y Whitney
authors.initials: YW
authors.lastname: Cheung
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, The Netherlands; Department of Internal Medicine, Maastricht University Medical Centre, P. Debyelaan 25, Maastricht, The Netherlands.
authors.forename: Annemieke C
authors.initials: AC
authors.lastname: Bouman
authors.affiliation: Department of Biochemistry, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, The Netherlands.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Castoldi
authors.affiliation: Department of Biochemistry, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, The Netherlands.
authors.forename: Simone J
authors.initials: SJ
authors.lastname: Wielders
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, The Netherlands.
authors.forename: Henri M H
authors.initials: HMH
authors.lastname: Spronk
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, The Netherlands; Department of Internal Medicine, Maastricht University Medical Centre, P. Debyelaan 25, Maastricht, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Ten Cate
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, The Netherlands; Department of Internal Medicine, Maastricht University Medical Centre, P. Debyelaan 25, Maastricht, The Netherlands.
authors.forename: Arina J
authors.initials: AJ
authors.lastname: Ten Cate-Hoek
authors.affiliation: Department of Internal Medicine, Flevohospital, Hospitaalweg 1, Almere, The Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Ten Wolde
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D054070:Postthrombotic Syndrome / Q000235:genetics*; D012008:Recurrence; D051217:Toll-Like Receptor 9 / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
keywords: Deep vein thrombosis; Post-thrombotic syndrome; Recurrent deep venous thrombosis; Residual thrombosis; Toll-like 9 receptor