Genetic variation in thrombin-activatable fibrinolysis inhibitor (TAFI) is associated with the risk of splanchnic vein thrombosis

Emile L. E. de Bruijne; Sarwa Darwish Murad; Moniek P. M. de Maat; Michael W. T. Tanck; Elizabeth B. Haagsma; Bart van Hoek; Frits R. Rosendaal; Harry L. A. Janssen; Frank W. G. Leebeek; for the Liver and Thrombosis Study Group

doi:10.1160/TH06-07-0407

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(02): 181-185
DOI: 10.1160/TH06-07-0407

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Genetic variation in thrombin-activatable fibrinolysis inhibitor (TAFI) is associated with the risk of splanchnic vein thrombosis

Authors

Emile L. E. de Bruijne

¹Departments of Hematology, Erasmus University Medical Center, Rotterdam
Sarwa Darwish Murad

²Departments of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam
Moniek P. M. de Maat

¹Departments of Hematology, Erasmus University Medical Center, Rotterdam
Michael W. T. Tanck

³Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam
Elizabeth B. Haagsma

⁴Department of Hepatogastroenterology, University Hospital Groningen, Groningen
Bart van Hoek

⁵Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden
Frits R. Rosendaal

⁶Department of Clinical Epidemiology and Hematology, Leiden University Medical Center, Leiden; The Netherlands
Harry L. A. Janssen

²Departments of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam
Frank W. G. Leebeek

¹Departments of Hematology, Erasmus University Medical Center, Rotterdam

for the Liver and Thrombosis Study Group

Abstract

Summary

Splanchnic vein thrombosis (SVT) has been associated with a hypercoagulable state. Thrombin-activatable fibrinolysis inhibitor (TAFI) may contribute to a hypercoagulable state, and therefore we were interested in the role of TAFI in SVT. Since the disease is frequently associated with liver insufficiency, which affects plasma levels ofTAFI, we studied the role of variation in theTAFI gene in SVT. In a multicenter case-control study on 118 patients with SVT (39 Budd-Chiari syndrome and 85 portal vein thrombosis) and 118 population-based controls, the relationship of SVT with single nucleotide polymorphisms (SNPs) and haplotypes in the TAFI gene (- 438G/A, Ala147Thr, Thr325Ile and 1583A/T) was determined. The risk for SVT was decreased (OR 0.2,95% CI 0.1–0.7) in 147Thr/Thr homozygotes and slightly,but not significantly,increased in carriers of the 325Ile allele (OR 1.6, 95%CI 0.9–2.7). Haplotype analysis confirmed that the Ala147Thr SNP has the strongest association with risk of SVT. In conclusion, genetic variation in the TAFI gene is associated with risk of SVT, suggesting a role for TAFI in the pathogenetic mechanism of SVT.

Keywords

Thrombin-activatable fibrinolysis inhibitor - Budd-Chiari syndrome - portal vein thrombosis - single nucleotide polymorphism - splanchnic vein thrombosis - inflammation - fibrinolysis

Full Text

References

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