title: PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects.
abstract: 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.
authors.affiliation: The Research Centre, La Fe University Hospital, Valencia, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Seguí
authors.forename: A
authors.initials: A
authors.lastname: Estellés
authors.forename: Y
authors.initials: Y
authors.lastname: Mira
authors.forename: F
authors.initials: F
authors.lastname: España
authors.forename: P
authors.initials: P
authors.lastname: Villa
authors.forename: C
authors.initials: C
authors.lastname: Falcó
authors.forename: A
authors.initials: A
authors.lastname: Vayá
authors.forename: S
authors.initials: S
authors.lastname: Grancha
authors.forename: F
authors.initials: F
authors.lastname: Ferrando
authors.forename: J
authors.initials: J
authors.lastname: Aznar
mesh_terms: D000328:Adult; D000941:Antigens / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D011401:Promoter Regions, Genetic; D011486:Protein C / Q000032:analysis; D012307:Risk Factors; D018709:Statistics, Nonparametric; D013917:Thrombin / Q000276:immunology; D019851:Thrombophilia / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014280:Triglycerides / Q000097:blood; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics* / Q000276:immunology
chemical_list: D000941:Antigens; D001786:Blood Glucose; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D014280:Triglycerides; D013917:Thrombin; D010959:Tissue Plasminogen Activator