A common 4G allele in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene as a risk factor for pulmonary embolism and arterial thrombosis in hereditary protein S deficiency
(1998) In Thrombosis and Haemostasis 79(4). p.802-807- Abstract
Reduced fibrinolytic capacity due to increased plasminogen activator inhibitor-1 (PAI-1) activity in plasma is a common finding in patients with coronary heart disease or venous thromboembolism, although its clinical significance is debated. Recently, a dimorphism in the PAI-1 promoter (4G-5G) has been reported and homozygosity for the 4G allele is associated with increased transcription and higher PAI-1 levels. Homozygous 4G genotype has been suggested to be a risk factor for myocardial infarction. In the present study, the 4G-5G dimorphism was determined in 349 individuals from 21 thrombophilic families with hereditary protein S deficiency and in 140 unrelated healthy controls. Among the 143 protein S deficient individuals, there was... (More)
Reduced fibrinolytic capacity due to increased plasminogen activator inhibitor-1 (PAI-1) activity in plasma is a common finding in patients with coronary heart disease or venous thromboembolism, although its clinical significance is debated. Recently, a dimorphism in the PAI-1 promoter (4G-5G) has been reported and homozygosity for the 4G allele is associated with increased transcription and higher PAI-1 levels. Homozygous 4G genotype has been suggested to be a risk factor for myocardial infarction. In the present study, the 4G-5G dimorphism was determined in 349 individuals from 21 thrombophilic families with hereditary protein S deficiency and in 140 unrelated healthy controls. Among the 143 protein S deficient individuals, there was no relationship between deep or superficial venous thrombosis and the PAI-1 dimorphism. However, 26% (12/46) of individuals having protein S deficiency combined with homozygosity for the 4G allele had suffered pulmonary embolism as compared to 7% (7/97) of protein S deficient individuals carrying at least one 5G allele (p = 0.0019). In protein S deficient individuals, arterial thrombosis was found to be associated with smoking and 4G homozygosity. No association was found between the PAI-1 dimorphism and arterial or venous thromboembolism in family members without protein S deficiency. In conclusion, the PAI-1 genotype affects the phenotypic expression of thrombophilia in protein S deficient individuals.
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- author
- Zöller, Bengt LU ; Garcia de Frutos, Pablo LU and Dahlbäck, B LU
- organization
- publishing date
- 1998-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- plasminogen activator inhibitor 1, protein S, adult, allele, article, controlled study, female, genotype, heart infarction, homozygosity, human, lung embolism, major clinical study, male, phenotype, priority journal, promoter region, protein S deficiency, risk factor, smoking, thrombosis, vein thrombosis
- in
- Thrombosis and Haemostasis
- volume
- 79
- issue
- 4
- pages
- 6 pages
- publisher
- Schattauer GmbH
- external identifiers
-
- pmid:9569196
- scopus:2642692693
- pmid:9569196
- ISSN
- 0340-6245
- language
- English
- LU publication?
- yes
- id
- fb44e327-8653-41ba-920d-8049c5d301d7
- date added to LUP
- 2017-10-19 15:10:49
- date last changed
- 2024-01-14 07:59:29
@article{fb44e327-8653-41ba-920d-8049c5d301d7, abstract = {{<p>Reduced fibrinolytic capacity due to increased plasminogen activator inhibitor-1 (PAI-1) activity in plasma is a common finding in patients with coronary heart disease or venous thromboembolism, although its clinical significance is debated. Recently, a dimorphism in the PAI-1 promoter (4G-5G) has been reported and homozygosity for the 4G allele is associated with increased transcription and higher PAI-1 levels. Homozygous 4G genotype has been suggested to be a risk factor for myocardial infarction. In the present study, the 4G-5G dimorphism was determined in 349 individuals from 21 thrombophilic families with hereditary protein S deficiency and in 140 unrelated healthy controls. Among the 143 protein S deficient individuals, there was no relationship between deep or superficial venous thrombosis and the PAI-1 dimorphism. However, 26% (12/46) of individuals having protein S deficiency combined with homozygosity for the 4G allele had suffered pulmonary embolism as compared to 7% (7/97) of protein S deficient individuals carrying at least one 5G allele (p = 0.0019). In protein S deficient individuals, arterial thrombosis was found to be associated with smoking and 4G homozygosity. No association was found between the PAI-1 dimorphism and arterial or venous thromboembolism in family members without protein S deficiency. In conclusion, the PAI-1 genotype affects the phenotypic expression of thrombophilia in protein S deficient individuals.</p>}}, author = {{Zöller, Bengt and Garcia de Frutos, Pablo and Dahlbäck, B}}, issn = {{0340-6245}}, keywords = {{plasminogen activator inhibitor 1; protein S; adult; allele; article; controlled study; female; genotype; heart infarction; homozygosity; human; lung embolism; major clinical study; male; phenotype; priority journal; promoter region; protein S deficiency; risk factor; smoking; thrombosis; vein thrombosis}}, language = {{eng}}, number = {{4}}, pages = {{802--807}}, publisher = {{Schattauer GmbH}}, series = {{Thrombosis and Haemostasis}}, title = {{A common 4G allele in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene as a risk factor for pulmonary embolism and arterial thrombosis in hereditary protein S deficiency}}, volume = {{79}}, year = {{1998}}, }