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Polymorphism of the plasminogen activator inhibitor type 1 gene, plasminogen level and thromboses in patients with the antiphospholipid syndrome

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Abstract

The frequency of venous and arterial thromboses and plasminogen level have been investigated in 78 patients with the antiphospholipid syndrome (APS), including 35 patients with systemic lupus erythematosus (SLE + APS) and 43 patients with primary APS (PAPS). The levels and genotypes of plasminogen activator inhibitor type 1 (PAI-1) were determined in 45 patients with APS (21 patients with SLE + APS and 24 patients with PAPS). A control group included 10 individuals without autoimmune disease signs and thromboses during the observation period and in anamnesis. It has been shown for the first time that for one third of 67 patients with APS and thromboses, high-positive levels of antiphospholipid antibodies (aPL) are associated with low plasminogen levels. The levels of PAI-1 antigen measured by the ELISA method, which detects active, latent and bound to plasminogen activator PAI-1, were compared with frequency of thromboses in APS patients. In one third of 43 patients with APS and thromboses the high and increased levels of PAI-1 were associated with high-positive aPL levels. One of possible mechanisms of this interrelationship was considered. It was shown that arterial and, to a greater extent, venous thromboses are associated with the 4G/5G polymorphism of the PAI-1 gene and high plasma level of the inhibitor in 79% of APS patients. In the presence of the 4G allele SLE + APS patients had higher PAI-1 levels than PAPS patients. The data obtained show that measuring the levels of plasminogen and PAI-1 as well as the 4G/5G polymorphism of the PAI-1 gene associated with thromboses may have the practical importance for identification of high risk of thrombosis in APS patients.

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Abbreviations

aCL:

anticardiolipin antibodies

AFK-pNA:

p-nitroanilide CHO-Ala-Phe-Lys

aPL:

antiphospholipid anibodies

APS:

antiphospholipid syndrome

aβ2GPI:

anti-β2-glycoprotein 1 antibodies

β2GPI:

β2-glycoprotein 1

GPL and MPL:

international assay units of anticardiolipin antibodies for IgG and IgM, respectively

LAC:

lupus anticoagulant

PAI-1:

plasminogen activator inhibitor-1

tPA:

tissue plasminogen activator

PAPS:

primary antiphospholipid syndrome

Pg:

plasminogen

SLE:

systemic lupus erythematosus

uPA:

urokinase-type plasminogen activator

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Authors and Affiliations

  1. Department of Chemistry, Lomonosov Moscow State University, Moscow, 119992, Russia

    R. B. Aisina, L. I. Mukhametova & S. D. Varfolomeyev

  2. Research Institute of Rheumatology of the Russian Academy of Medical Sciences, Moscow, Russia

    E. V. Ostryakova, N. V. Seredavkina, T. M. Reshetnyak & E. L. Nasonov

  3. Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia

    L. I. Patrushev & N. L. Patrusheva

  4. Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow, Russia

    D. A. Gulin & K. B. Gershkovich

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  1. R. B. Aisina
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  2. L. I. Mukhametova
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  3. E. V. Ostryakova
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Original Russian Text © R.B. Aisina, L.I. Mukhametova, E.V. Ostryakova, N.V. Seredavkina, L.I. Patrushev, N.L. Patrusheva, T.M. Reshetnyak, D.A. Gulin, K.B. Gershkovich, E.L. Nasonov, S.D. Varfolomeyev, 2013, published in Biomeditsinskaya Khimiya.

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Aisina, R.B., Mukhametova, L.I., Ostryakova, E.V. et al. Polymorphism of the plasminogen activator inhibitor type 1 gene, plasminogen level and thromboses in patients with the antiphospholipid syndrome. Biochem. Moscow Suppl. Ser. B 7, 1–15 (2013). https://doi.org/10.1134/S1990750813010010

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