RGD Reference Report - Plasminogen activator inhibitor-1 4G/5G polymorphism, factor V Leiden, prothrombin mutations and the risk of VTE recurrence. - Rat Genome Database

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

Authors: Sundquist, K  Wang, X  Svensson, PJ  Sundquist, J  Hedelius, A  Larsson Lonn, S  Zoller, B  Memon, AA 
Citation: Sundquist K, etal., Thromb Haemost. 2015 Nov 25;114(6):1156-64. doi: 10.1160/TH15-01-0031. Epub 2015 Aug 6.
RGD ID: 11536892
Pubmed: (View Article at PubMed) PMID:26245493
DOI: Full-text: DOI:10.1160/TH15-01-0031

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 Malmo 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.



Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
F5  (coagulation factor V)

Genes (Mus musculus)
F5  (coagulation factor V)

Genes (Homo sapiens)
F5  (coagulation factor V)


Additional Information