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Identification of Genetic Aberrations in Thrombomodulin Gene in Patients with Recurrent Venous Thromboembolism

  • Abrar Ahmad
  • Kristina Sundquist
  • Bengt Zöller
  • Peter J. Svensson
  • Jan Sundquist
  • Ashfaque A. Memon
Publishing year: 2017-05-01
Language: English
Pages: 319-328
Publication/Series: Clinical and Applied Thrombosis/Hemostasis
Volume: 23
Issue: 4
Document type: Journal article
Publisher: SAGE Publications Inc.

Abstract english

Thrombomodulin (THBD) serves as a cofactor for thrombin-mediated activation of anticoagulant protein C pathway. Genetic aberrations in THBD have been studied in arterial and venous thrombosis. However, genetic changes in THBD and their role in the risk assessment of recurrent venous thromboembolism (VTE) are not well understood. The aim of the present study was to identify the genetic aberrations in THBD and their association with the risk of VTE recurrence in a prospective population-based study. We sequenced the entire THBD gene, first in selected patients with VTE (n = 95) by Sanger sequencing and later validated those polymorphisms with minor allele frequency (MAF) ≥5% in the whole study population (n = 1465 with the follow-up period of 1998-2008) by Taqman polymerase chain reaction. In total, we identified 8 polymorphisms in THBD, and 3 polymorphisms with MAF ≥5% were further validated. No significant association between THBD polymorphisms and risk of VTE recurrence on univariate or multivariate Cox regression analysis was found (hazard ratio [HR] = 0.89, 95% confidence interval [CI] = 0.62-1.28, HR = 1.27, 95% CI = 0.88-1.85, and HR = 1.15, 95% CI = 0.80-1.66 for THBD rs1962, rs1042580, and rs3176123 polymorphisms, respectively), adjusted for family history, acquired risk factors for VTE, location of deep vein thrombosis, and risk of thrombophilia. Subanalysis of patients with unprovoked first VTE also showed no significant association of identified THBD polymorphisms with the risk of VTE recurrence. Our results show that aberrations in the THBD gene may not be useful for the assessment of VTE recurrence; however, further studies with large sample size are needed to confirm these findings.


  • Cardiac and Cardiovascular Systems
  • anticoagulant therapy
  • multivariate analysis
  • recurrent VTE


  • Family Medicine, Psychiatric Epidemiology and Migration
  • Family Medicine, Cardiovascular Epidemiology and Lifestyle
  • Clinical Coagulation, Malmö
  • ISSN: 1076-0296
E-mail: abrar [dot] ahmad [at] med [dot] lu [dot] se

Assistant researcher

Diabetic Complications


Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00