Plasminogen activator inhibitor-1 4G/5G polymorphism, factor V Leiden, prothrombin mutations and the risk of VTE recurrence

Kristina Sundquist; Xiao Wang; Peter J. Svensson; Jan Sundquist; Anna Hedelius; Sara Larsson Lönn; Bengt Zöller; Ashfaque A. Memon

doi:10.1160/TH15-01-0031

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 114(06): 1156-1164
DOI: 10.1160/TH15-01-0031

Coagulation and Fibrinolysis

Schattauer GmbH

Plasminogen activator inhibitor-1 4G/5G polymorphism, factor V Leiden, prothrombin mutations and the risk of VTE recurrence

Authors

Kristina Sundquist

¹Center for Primary Care Research, Lund University, Malmo, Sweden

²Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California, USA
Xiao Wang

¹Center for Primary Care Research, Lund University, Malmo, Sweden
Peter J. Svensson

³Clinical Coagulation Research Unit, Lund University, Malmo, Sweden
Jan Sundquist

¹Center for Primary Care Research, Lund University, Malmo, Sweden

²Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California, USA
Anna Hedelius

¹Center for Primary Care Research, Lund University, Malmo, Sweden
Sara Larsson Lönn

¹Center for Primary Care Research, Lund University, Malmo, Sweden
Bengt Zöller

¹Center for Primary Care Research, Lund University, Malmo, Sweden
Ashfaque A. Memon

¹Center for Primary Care Research, Lund University, Malmo, Sweden

Abstract

Summary

Plasminogen-activator inhibitor (PAI)-1 is an important inhibitor of the plasminogen/plasmin system. PAI-1 levels are influenced by the 4G/5G polymorphism in the PAI-1 promoter. We investigated the relationship between the PAI-1 polymorphism and VTE recurrence, and its possible modification by factor V Leiden (FVL) and prothrombin (PTM) mutations. Patients (n=1,069) from the Malmö Thrombophilia Study were followed from discontinuation of anticoagulant treatment until diagnosis of VTE recurrence or the end of the study (maximum follow-up 9.8 years). One hundred twenty-seven patients (11.9 %) had VTE recurrence. PAI-1 was genotyped by TaqMan PCR. Cox regression analysis adjusted for age, sex and acquired risk factors of VTE showed no evidence of an association between PAI-1 genotype and risk of VTE recurrence in the study population as a whole. However, by including an interaction term in the analysis we showed that FVL but not PTM modified the effect of PAI-1 genotype: patients with the 4G allele plus FVL had a higher risk of VTE recurrence [hazard ratio (HR) =2.3, 95 % confidence interval (CI) =1.5–3.3] compared to patients with the 4G allele but no FVL (reference group) or FVL irrespective of PAI-1 genotype (HR=1.8, 95 % CI=1.3–2.5). Compared to reference group, 5G allele irrespective of FVL was associated with lower risk of VTE recurrence only when compared with 4G allele together with FVL. In conclusion, FVL has a modifying effect on PAI-1 polymorphism in relation to risk of VTE recurrence. The role of PAI-1 polymorphism as a risk factor of recurrent VTE may be FVL dependent.

Keywords

Fibrinolysis - plasminogen - PAI-1 polymorphism - recurrence - venous thromboembolism

Full Text

References

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