title: The PAI-1 gene 4G/5G polymorphism and deep vein thrombosis in patients with inherited thrombophilia.
abstract: Genetic and acquired factors may influence phenotypic expression of inherited thrombophilia. Hypofibrinolysis due to excess PAI-1 can be found in patients with deep vein thrombosis (DVT) and 4G/5G polymorphism of the PAI-1 gene may modulate the inhibitor's synthesis. In 149 patients with inherited thrombophilia, the possible thrombotic contribution of both 4G/5G polymorphism and PAI-1 plasma levels was evaluated. Sixty-seven patients with idiopathic DVT and 98 normal subjects were also studied. By comparison with controls, a significantly higher prevalence of 4G/4G genotype was seen in idiopathic DVT and in thrombophilia patients, although in this latter group the difference only remained significant in cases symptomatic for thrombosis (p = 0.01). The 4G/4G genotype was associated with a greater risk of thrombosis both in symptomatic thrombophilia patients (OR 2.85, 95% CI 1.26-6.46) and in idiopathic DVT patients (OR 3.1, 95% CI 1.26-7.59). The greater frequency of 4G allele in symptomatic thrombophilia patients with respect to controls was statistically significant (p = 0.04). Compared to healthy subjects, PAI-1:Ag levels were higher in symptomatic thrombophilia patients and related to the 4G/5G polymorphism, with significantly higher values in the 4G/4G carriers. In conclusion, PAI-1 4G/5G polymorphism may influence PAI-1 expression and thrombotic risk in patients with inherited thrombophilia.
authors.affiliation: Department of Medical and Surgical Sciences, University of Padua Medical School, Padua, Italy. mtsart@unipd.it
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sartori
authors.forename: Cristina
authors.initials: C
authors.lastname: Danesin
authors.forename: Graziella
authors.initials: G
authors.lastname: Saggiorato
authors.forename: Daniela
authors.initials: D
authors.lastname: Tormene
authors.forename: Paolo
authors.initials: P
authors.lastname: Simioni
authors.forename: Luca
authors.initials: L
authors.lastname: Spiezia
authors.forename: Giovanni Maurizio
authors.initials: GM
authors.lastname: Patrassi
authors.forename: Antonio
authors.initials: A
authors.lastname: Girolami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D019851:Thrombophilia / Q000097:blood / Q000150:complications / Q000235:genetics*; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics*
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1