Document Detail


4G/5G polymorphism of PAI-1 gene promoter and fibrinolytic capacity in patients with deep vein thrombosis.
MedLine Citation:
PMID:  9869167     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 gene has been suggested to be involved in regulation of the synthesis of the inhibitor, the 4G allele being associated with enhanced gene expression. A relationship between 4G/5G polymorphism and PAI-1 levels was found in patients with cardiovascular and metabolic diseases, but not in healthy subjects. In the present work we studied the distribution of PAI-1 4G/5G genotype and its relation to fibrinolytic capacity in 70 unrelated patients with deep vein thrombosis. Each patient was assayed before and after 20 min. Venous occlusion for euglobulin lysis time, t-PA antigen and activity, and PAI-1 antigen and activity. The prevalence of 5G homozygous carriers was significantly lower in patients than in controls (10% vs. 26%, p=0.009). The 5G allele frequency was reduced, even though not significantly, in DVT patients compared to healthy subjects (0.40 vs. 0.51, respectively). In the patient group, the mean PAI-1 antigen and activity levels were significantly higher than among controls and related to the 4G/5G polymorphism. In patients with 4G/5G and 4G/4G genotype a significant correlation was found between PAI-1 levels and the global fibrinolytic activity as evaluated by euglobulin lysis time. The prevalence of a reduced fibrinolytic potential due to PAI-1 excess was 45.7% among DVT patients. Moreover, the prevalence of PAI-1 induced hypofibrinolysis was strongly related to PAI-1 polymorphism, since it was significantly lower in 5G homozygous patients (28.6%) than in both 4G/5G carriers (55.3%, p <0.001) and 4G homozygous patients (57.9%, p <0.001). In conclusion, in patients with deep vein thrombosis the 4G polymorphism of PAI-1 gene promoter may influence the expression of PAI-1 and it should be taken into consideration as a facilitating condition for pathological fibrinolysis together with other environmental and genetic factors. Whether this has any significance in regard to the pathogenesis of venous thrombosis remains to be proven.
Authors:
M T Sartori; B Wiman; S Vettore; F Dazzi; A Girolami; G M Patrassi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  80     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1999-04-15     Completed Date:  1999-04-15     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  956-60     Citation Subset:  IM    
Affiliation:
Institute of Medical Semeiotics, II Chair of Internal Medicine, University of Padua Medical School, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Alleles
Blood Coagulation Tests
Female
Fibrinolysis / genetics*
Gene Expression Regulation
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
Mutagenesis, Insertional
Plasminogen Activator Inhibitor 1 / genetics*
Polymorphism, Genetic*
Promoter Regions, Genetic / genetics*
Sequence Deletion
Thrombophilia / genetics
Thrombophlebitis / blood,  genetics*
Tissue Plasminogen Activator / analysis
Chemical
Reg. No./Substance:
0/Plasminogen Activator Inhibitor 1; EC 3.4.21.68/Tissue Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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