PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects

• Published in: British journal of haematology Vol. 111; no. 1; pp. 122 - 128
• Main Authors: SEGU, Rafael, ESTELLES, Amparo, MIRA, Yolanda, ESPANA, Francisco, VILLA, Piedad, FALCO, Cristina, VAYA, Amparo, GRANCHA, Salvador, FERRANDO, Fernando, AZNAR, Justo
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.10.2000; Blackwell Publishing Ltd
• Subjects: Adult; Antigens - analysis; Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - analysis; Cardiology. Vascular system; Case-Control Studies; Chi-Square Distribution; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Genetic Predisposition to Disease; Genotype; Hematology; Humans; Male; Medical sciences; Middle Aged; Plasminogen Activator Inhibitor 1 - analysis; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - immunology; Promoter Regions, Genetic; Protein C - analysis; Risk Factors; Statistics, Nonparametric; Thrombin - immunology; Thrombophilia - genetics; Tissue Plasminogen Activator - analysis; Triglycerides - blood; Venous Thrombosis - blood; Venous Thrombosis - genetics; Venous Thrombosis - immunology; Human; Genetic variability; Transcription promoter; Cardiovascular disease; Genotype; Hemopathy; Epidemiology; Thrombosis; Venous disease; Vascular disease; Thrombophilia; Plasminogen activator inhibitor 1; Gene; Risk factor; Genetics; Deep vein; Coagulopathy; Public health; Polymorphism
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2000.02321.x

Impaired fibrinolysis as a result of increased plasminogen activator inhibitor-1 (PAI-1) levels in plasma is a common finding in patients with deep vein thrombosis (DVT). A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to influence the levels of PAI-1. The 4G allele was found to be associated with higher plasma PAI-1 activity (act), but contradictory results on the incidence of the 4G allele in DVT patients have been reported. The aim of this study was to analyse whether the PAI-1 promoter 4G/5G genotype increases the risk of venous thrombosis in subjects with thrombophilic defects, and to determine the distribution of the PAI-1 4G/5G genotype and its relation to plasma PAI-1 levels in 190 unrelated patients with DVT in comparison with a control group of 152 healthy subjects. No differences between the 4G/5G allele distribution in the DVT group (0.43/0.57) and in the control group (0.42/0.58) were observed. However, the presence of the 4G allele significantly increased the risk of thrombosis in patients with other thrombophilic defects. Significantly higher PAI-1 levels were observed in DVT patients than in the controls. Our results also showed significant differences in the plasma levels of PAI-1 antigen (ag) and PAI-1 act among the 4G/5G genotypes in DVT patients. A multivariate analysis revealed that, in the DVT group, PAI-1 ag levels were influenced by the 4G allele dosage, triglyceride levels and body mass index (BMI). The influence of the 4G allele dosage on PAI-1 levels was independent of the triglyceride levels and BMI. In the control group, no significant correlation between PAI-1 levels and 4G allele dosage was observed. In conclusion, the PAI-1 promoter polymorphism was found to have an influence on PAI-1 levels in DVT patients and on the risk of venous thrombosis in subjects with other genetic thrombophilic defects.