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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

Zöller, Bengt LU orcid ; Garcia de Frutos, Pablo LU and Dahlbäck, B LU (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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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}},
}