title: Promotor polymorphisms of plasminogen activator inhibitor-1 and other thrombophilic genotypes in cerebral venous thrombosis: a case-control study in adults.
abstract: Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activator. A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to enhance the plasma levels of PAI-1. In particular, the 4G allele (guanosine deletion) has been linked with increased plasma PAI-1 levels, which may lead to impaired activity of the fibrinolytic system, thus increasing the incidence of thrombotic events. The aim of this case-control study was to analyze whether variants of the PAI-1 promotor genotype 4G/4G, 4G/5G and 5G/5G, in particular the 4G/5G-variant, constitute an independent risk factor of cerebral venous thrombosis (CVT). A total of 136 consecutive patients with proven CVT were compared to 1,054 DNA specimens of healthy controls from a population-based cohort. PAI-1 promotor polymorphisms were evaluated using polymerase chain reaction. No significant association of CVT with PAI-1 4G/5G was found in either the additive (OR 1.04; 95 % CI 0.78-1.38) or in the dominant model (OR 1.24; 95 % CI 0.72-2.13). Also, the prevalence of the other genotypes (4G/4G and 5G/5G) in patients was not significantly different from controls. When considering the variants of the PAI-1 promoter genotype in combination with known genetical thrombophilias, no differences were found either. As was expected, the prothrombin (G20210A) genotype was confirmed as an independent risk factor for CVT. We conclude that the 4G allele of the PAI-1 polymorphism does not increase the risk of CVT in adults.
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich-Heine-University, Moorenstraße 5, 40225, Düsseldorf, Germany. Marius.Ringelstein@med.uni-duesseldorf.de
authors.forename: Marius
authors.initials: M
authors.lastname: Ringelstein
authors.forename: Alexander
authors.initials: A
authors.lastname: Jung
authors.forename: Klaus
authors.initials: K
authors.lastname: Berger
authors.forename: Monika
authors.initials: M
authors.lastname: Stoll
authors.forename: Katharina
authors.initials: K
authors.lastname: Madlener
authors.forename: Christof
authors.initials: C
authors.lastname: Klötzsch
authors.forename: Felix
authors.initials: F
authors.lastname: Schlachetzki
authors.forename: Erwin
authors.initials: E
authors.lastname: Stolz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D020767:Intracranial Thrombosis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020246:Venous Thrombosis / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human