Abstract
The FII c.1787G>A (prothrombin Belgrade) is a novel prothrombotic mutation which leads to impaired inhibition of thrombin by antithrombin (antithrombin resistance). So far, the mechanism of this variant has not been fully elucidated. To investigate the effect of FII c.1787G>A mutation on the prothrombin gene expression, its functional analysis was performed in vitro. By Real-Time PCR, expression levels of FII gene variants were evaluated in Cos-7 cells transiently transfected with c.1787G (wild-type) and c.1787A prothrombin expression vectors, with no differences observed. The relative quantification of prothrombin protein amounts was accomplished by Western blot analysis, also with no differences observed. Therefore, the mechanism of FII c.1787G>A mutation does not alter prothrombin expression profile.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Colman R., Marder V., Clowes A., George J., Goldhaber S. 2006. Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 5th ed. Philadelphia: Lippincott Williams & Wilkins.
Naess I.A., Christiansen S.C., Romundstad P., Cannegieter S.C., Rosendaal F.R., Hammerstrom J. 2007. Incidence and mortality of venous thrombosis: A population-based study. J. Thromb. Haemost. 5, 692–699.
Miyawaki Y., Suzuki A., Fujita J., Maki A., Okuyama E., Murata M., Takagi A., Murate T., Kunishima S., Sakai M., Okamoto K., Matsushita T., Naoe T., Saito H., Kojima T. 2012. Thrombosis from a prothrombin mutation conveying antithrombin resistance. N. Engl. J. Med. 366, 2390–2396.
Bode W., Turk D., Karshikov A. 1992. The refined 1.9-Å X-ray crystal structure of D-Phe-Pro-Argchloromethyl ketone-inhibited human alpha-thrombin: Structure analysis, overall structure, electrostatic properties, detailed active-site geometry, and structure–function relationships. Protein Sci. 1, 426–471.
Djordjevic V., Kovac M., Miljic P., Murata M., Takagi A., Pruner I., Francuski D., Kojima T., Radojkovic D. 2013. A novel prothrombin mutation in two families with prominent thrombophilia: The first cases of antithrombin resistance in a Caucasian population. J. Thromb. Haemost. 11, 1936–1939.
Kishimoto M., Suzuki N., Murata M., Ogawa M., Kanematsu T., Takagi A., Kiyoi H., Kojima T., Matsushita T. 2016. The first case of antithrombin-resistant prothrombin Belgrade mutation in Japanese. Ann. Hematol. 95 (3), 541–542. doi 10.1007/s00277-015-2533-6
Ljujic M., Divac-Rankov A., Kojic S., Miranda E., Radojkovic D. 2014. Functional analysis of novel alpha-1 antitrypsin variants G320R and V321F. Mol. Biol. Rep. 41, 6133–6141.
Kaplan J., Land S. 2005. Influence of maternal-fetal histocompatibility and MHC zygosity on maternal microchimerism. J. Immunol. 174, 7123–7128.
Kovac M., Elezovic I., Mikovic Z., Mandic V., Djordjevic V., Radojkovic D., Lalic-Cosic S., Murata M., Takagi A., Kojima T. 2015. High prophylactic LMWH dose successfully suppressed hemostatic activation in pregnant woman with a new prothrombin c.1787G>A mutation. Thromb. Res. 135, 420–422.
Di Cera E., Guinto E.R., Vindigni A., Dang Q.D., Ayala Y.M., Wuyi M., Tulinsky A. 1995. The Na+ binding site of thrombin. J. Biol. Chem. 270, 22089–22092.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published in Russian in Molekulyarnaya Biologiya, 2017, Vol. 51, No. 1, pp. 59–63.
The article is published in the original.
Rights and permissions
About this article
Cite this article
Gvozdenov, M., Pruner, I., Tomic, B. et al. The effect of FII c.1787G>A (prothrombin Belgrade) mutation on prothrombin gene expression in vitro. Mol Biol 51, 49–52 (2017). https://doi.org/10.1134/S0026893316060078
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S0026893316060078