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Promotor polymorphisms of plasminogen activator inhibitor-1 and other thrombophilic genotypes in cerebral venous thrombosis: a case-control study in adults

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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.

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Acknowledgments

The authors appreciate the help of Prof. Dr. med. Orhan Aktas, Duesseldorf in reviewing the manuscript.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Neurology, Medical Faculty, Heinrich-Heine-University, Moorenstraße 5, 40225, Düsseldorf, Germany

    Marius Ringelstein

  2. Department of Neurology, University Hospital Münster, Münster, Germany

    Alexander Jung

  3. Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany

    Klaus Berger

  4. Leibniz Institute of Arteriosclerosis Research, University of Münster, Münster, Germany

    Monika Stoll

  5. Department of Haemostaseology, Kerckhoff-Klinik, Bad Nauheim, Germany

    Katharina Madlener

  6. Department of Neurology, Hegau-Bodensee-Klinikum, Singen, Germany

    Christof Klötzsch

  7. Department of Neurology, University Hospital Regensburg, Regensburg, Germany

    Felix Schlachetzki

  8. Department of Neurology, CaritasKlinikum St. Theresia, Saarbrücken, Germany

    Erwin Stolz

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  1. Marius Ringelstein
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  2. Alexander Jung
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Correspondence to Marius Ringelstein.

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M. Ringelstein and A. Jung contributed equally to this work.

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Ringelstein, M., Jung, A., Berger, K. et al. Promotor polymorphisms of plasminogen activator inhibitor-1 and other thrombophilic genotypes in cerebral venous thrombosis: a case-control study in adults. J Neurol 259, 2287–2292 (2012). https://doi.org/10.1007/s00415-012-6477-7

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  • DOI: https://doi.org/10.1007/s00415-012-6477-7

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