Plasminogen activator inhibitor-1 4G/5G polymorphism, factor V Leiden, prothrombin mutations and the risk of VTE recurrence.
Sundquist, Kristina LU ; Wang, Xiao LU ; Svensson, Peter LU ; Sundquist, Jan LU ; Hedelius, Anna LU ; Larsson Lönn, Sara LU ; Zöller, Bengt LU
and Memon, Ashfaque
LU
(2015)
In Thrombosis and Haemostasis
114(6).
p.1156-1164
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7844634
- author
- Sundquist, Kristina
LU
; Wang, Xiao
LU
; Svensson, Peter
LU
; Sundquist, Jan
LU
; Hedelius, Anna
LU
; Larsson Lönn, Sara
LU
; Zöller, Bengt
LU
and Memon, Ashfaque
LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Thrombosis and Haemostasis
- volume
- 114
- issue
- 6
- pages
- 1156 - 1164
- publisher
- Schattauer GmbH
- external identifiers
-
- pmid:26245493
- wos:000365769200009
- pmid:26245493
- scopus:84983203355
- ISSN
- 0340-6245
- DOI
- 10.1160/TH15-01-0031
- project
- Identification of diagnostic and prognostic biomarkers of venous thromboembolism and its recurrence
- Genetic risk factor of venous thromboembolism and its recurrence
- language
- English
- LU publication?
- yes
- id
- 94edb7b7-deb5-4691-8104-5012d0617de8 (old id 7844634)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26245493?dopt=Abstract
- date added to LUP
- 2016-04-01 14:21:01
- date last changed
- 2022-04-30 01:18:20
@article{94edb7b7-deb5-4691-8104-5012d0617de8,
abstract = {{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.}},
author = {{Sundquist, Kristina and Wang, Xiao and Svensson, Peter and Sundquist, Jan and Hedelius, Anna and Larsson Lönn, Sara and Zöller, Bengt and Memon, Ashfaque}},
issn = {{0340-6245}},
language = {{eng}},
number = {{6}},
pages = {{1156--1164}},
publisher = {{Schattauer GmbH}},
series = {{Thrombosis and Haemostasis}},
title = {{Plasminogen activator inhibitor-1 4G/5G polymorphism, factor V Leiden, prothrombin mutations and the risk of VTE recurrence.}},
url = {{https://lup.lub.lu.se/search/files/3926285/8868088.pdf}},
doi = {{10.1160/TH15-01-0031}},
volume = {{114}},
year = {{2015}},
}