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"Институт токсикологии Федерального медико-биологического агентства"
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Институт теоретической и экспериментальной биофизики Российской академии наук.

ООО "ИЦ КОМКОН".




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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

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«
Vol. 16, Art. 71 (pp. 766-778)    |    2015       
»

Genetic risk factors of thrombosis and oxidant-antioxidant system in patients with polycythemia vera
Aleksanyan L.R., Ribakova L.P., Kapustin S.I., Zamotina T.B., Bessmeltsev S.S.

Russian Research Institute of Hematology and Transfusiology,
Russian Federal Medico-biological Agency



Brief summary

Prophylaxis of vascular complications is an important part of modern therapy in polycythemia vera (PV). Identification of genetic and acquired risk factors for thrombosis in PV is of great value. In this work, we studied the frequency of several genetic variants associated with thrombosis as well as the peculiarities of oxidant-antioxidant system (OS-AOS) in 100 patients with PV and 200 healthy controls (HC). We found, that mutations FV G1691A and FII G20210A are not associated with increased risk of thrombotic complications in PV. We revealed almost 2-fold decrease in frequency of PAI-1 5G/5G genotype in the group of PV patients with positive history of thrombosis when compared to those free of thrombotic events. This variant of PAI-1 gene could, thus, have protective effect on thrombosis development in PV. We also found, that distribution of genotypes of the β-fibrinogen (factor I), GpIIIa and MTHFR genes as well as their combinations in PV group differed from those in HC. The features of imbalance between oxidant and antioxidant systems were detected in PV patients. This observation could indicate on participation of this acquired factor in pathogenesis of thrombotic and other complications in PV. The growth of oxidation processes was reflected by 40% increase of malondialdehyde content in blood plasma of PV patients (15.4 μmol/l vs. 11.0 μmol/l in HC, (р<0,001). At the same time, the level or/and activity of several components of the antioxidant system were decreased significantly in PV group. In particular, we detected the reduction of ceruloplasmin plasma level (by 30% compared to HC, р<0,01) and non-protein thiol groups content in erythrocytes (by 41% compared to HC, р<0,001) in PV patients. Moreover, the mean ratio of superoxide dismutase to catalase activities was significantly decreased in PV group (р<0,001).


Key words

polycythemia vera, thrombosis, risk factor, inherited thrombophilia, gene, oxidative stress, oxidant-antioxidant system





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