Biopolym. Cell. 2010; 26(4):299-305.
Molecular Biomedicine
Ischemic stroke in Ukrainian population: possible involvement of the F2 G20210A, F5 G1691A and MTHFR C677T gene variants
- Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 - Gerontology Institute of the Academy of Medical Sciences of Ukraine
67, Vyshgorodska Str., Kyiv, Ukraine, 04114 - Taras Shevchenko National University of Kyiv
64, Volodymyrska Str., Kyiv, Ukraine, 01601
Abstract
Aim. To evaluate a possible involvement of the F2, F5, MTHFR gene variants into ischemic stroke pathogenesis in population of Ukraine. Methods. Polymorphic variants were analyzed in unrelated 183 stroke patients, 100 individuals from the general population of Ukraine and 88 healthy individuals elder than 65 years using PCR followed by RFLP analysis. Results. Unfavourable polymorphic variants F2 20210A, F5 1691A and MTHFR 677T were observed more frequently in patients with ischemic stroke comparing to control groups. Conclusions. F5 1691A and MTHFR 677T polymorphic variants are associated with the occurrence of ischemic stroke in women. F2 20210A is associated with the occurrence of ischemic stroke in men. Cumulative risk factor for stroke development is revealed in a combination of unfavorable polymorphic variants 20210A, 1691A and 677T of F2, F5 and MTHFR genes.
Keywords: Factor V Leiden (F5 G1691A) gene, prothrombin (F2 G20210A) gene, methylenetetrahydrofolate reductase (MTHFR C677T) gene, ischemic stroke, combined genotype
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References
[1]
Madonna P., de Stefano V., Coppola A., Cirillo F., Cerbone A. M., Orefice G., Di Minno G. Hyperhomocysteinemia and other inherited prothrombotic conditions in young adults with a history of ischemic stroke Stroke 2002 33, N 1:51– 56.
[2]
Meyer M. R., Haas E., Barton M. Gender differences of cardiovascular disease: new perspectives for estrogen receptor signaling Hypertension 2006 47, N 6:1019–1026.
[4]
Margaglione M., D'Andrea G., Giuliani N., Brancaccio V., De Lucia D., Grandone E., De Stefano V., Tonali P. A., Di Minno G. Inherited prothrombotic conditions and premature ischemic stroke: sex difference in the association with factor V Leiden Artherioscler. Thromb. Vasc. Biol 1999 19, N 7:1751–1756.
[5]
De Stefano V., Chiusolo P., Paciaroni K., Casorelli I., Rossi E., Molinari M., Servidei S., Tonali P. A., Leone G. Prothrombin G20210A mutant genotype is a risk factor for cerebrovascular ischemic disease in young patients Blood 1998 91, N 10:3562–3565.
[6]
Lalouschek W., Schillinger M., Hsieh K., Endler G., Tentschert S., Lang W., Cheng S., Mannhalter C. Matched casecontrol study on factor V Leiden and the prothrombin G20210A mutation in patients with ischemic stroke/transient ischemic attack up to the age of 60 years Stroke 2005 36, N 7:1405–1409.
[7]
Bertina R. M., Koeleman B. P., Koster T., Rosendaal F. R., Dirven R. J., de Ronde H., van der Velden P. A., Reitsma P. H. Mutation in blood coagulation factor V associated with resistance to activated protein C Nature 1994 369, N 6475 P. 64–67.
[8]
Ridker P. M., Hennekens C. H., Lindpaintner K., Stampfer M. J., Eisenberg P. R., Miletich J. P. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men N. Engl. J. Med 1995 332, N 14:912–917.
[9]
Poort S. R., Rosendaal F. R., Reitsma P. H., Bertina R. A common genetic variation in the 39-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and increase in venous thrombosis Blood 1996 88, N 10:3698–3703.
[10]
Maniatis T., Fritsch E. F., Sambrook J. Molecular cloning: a laboratory manual New York: Cold Spring Harbor Lab. publ., 1982 545 p.
[11]
Koksal V., Baris I., Etlik O. Primer-engineered multiplex PCR–RFLP for detection of MTHFR C677T, prothrombin G20210A and factor V Leiden mutations Exp. Mol. Pathol 2007 83, N 1:1–3.
[12]
Michael S., Qamar R., Akhtar F., Khan W. A., Ahmed A. C677T polymorphism in the methylenetetrahydrofolate reductase gene is associated with primary closed angle glaucoma. Mol. Vis. 2008; 14:661–665.
[13]
Moore J. H. Computational analysis of gene-gene interactions using multifactor dimensionality reduction Expert Rev. Mol. Diagnost 2004 4, N 6:795–803.
[14]
Raymond M., Rousset F. GENEPOP (version 1.2): population genetics software for exact tests and ecumenicism J. Hered. 1995; 86, N 3:248–249.
[15]
Excoffier L., Laval G., Schneider S. Arlequin ver. 3.0: An integrated software package for population genetics data analysis. Evol. Bioinform. Online 2005; 1:47–50.
[16]
Henkens C., Bom V., Seinen A., van der Meer J. Sensitivity to activated protein C: influence of oral contraceptives and sex. Thromb. Haemost. 1995; 73, N 3:402–404.
[17]
Jensen-Urstad K., Johansson J. Gender difference in age-related changes in vascular function J. Int. Med 2001 250, N 1:29–36.
[18]
Stampfer M. J., Colditz G. A., Willett W. C. Menopause and heart disease. A review Ann. N. Y. Acad. Sci 1990 592:193–203.
[19]
Koledova V. V., Khalil R. A. Sex hormone replacement therapy and modulation of vascular functionin cardiovascular disease Expert Rev. Cardiovasc. Ther 2007 5, N 4 P. 777–789.
[20]
Orshal J. M., Khalil R. A. Gender, sex hormones, and vascular tone Am. J. Physiol. Regul. Integr. Comp. Physiol 2004 286, N 2:R233–R249.
[21]
Otsuki M., Gao H., Dahlman-Wright K., Ohlsson C., Eguchi N., Urade Y., Gustafsson J. A. Specific regulation of lipocalin-type prostaglandin D synthase in mouse heart by estrogen receptor beta Mol. Endocrinol 2003 17, N 9:1844– 1855.
[22]
Di Carlo C., Di Spiezio Sardo A., Bifulco G., Tommaselli G. A., Guerra G., Rippa E., Mandato V. D., Nappi C. Postmenopausal hypoestrogenism increases vasoconstrictor neuropeptides and decreases vasodilator neuropeptides content in arterial-wall autonomic terminations Fertil. Steril 2007 88, N 1:95–99.
[23]
Gopel W., Ludwig M., Junge A. K., Kohlmann T., Diedrich K., Moller J. Selection pressure for the factor-V-Leiden mutation and embryo implantation Lancet 2001 358, N 9289:1238–1239.
[25]
Lindqvist P. G., Zoller B., Dahlback B. Improved hemoglobin status and reduced menstrual blood loss among female carriers of factor V Leiden an evolutionary advantage? Thromb. Haemost 2001 86, N 4:1122–1123.
[26]
Liu P. Y., Death A. K., Handelsman D. J. Androgens and cardiovascular disease Endocrinol. Rev 2003 24, N 3 P. 313–340.
[27]
Traish A. M., Saad F., Feeley R. J., Guay A. The dark side of testosterone deficiency: III. Cardiovascular disease J. Androl 2009 30, N 5:477–494.
[28]
Russo G. T., Friso S., Jacques P. F., Rogers G., Cucinotta D., Wilson P. W., Ordovas J. M., Rosenberg I. H., Selhub J. Framingham Offspring Study Cohort. Age and gender affect the relation between methylenetetrahydrofolate reductase C677T genotype and fasting plasma homocysteine concentrations in the Framingham Offspring Study Cohort. J. Nutr 2003 133, N 11:3416–3421.
[29]
Dierkes J., Jeckel A., Ambrosch A., Westphal S., Luley C., Boeing H. Factors explaining the difference of total homocysteine between men and women in the European Investigation Into Cancer and Nutrition Potsdam Study Metabolism 2001 50, N 6:640–645.
[30]
Woo K. S., Chook P., Lolin Y. I., Cheung A. S., Chan L. T., Sun Y. Y., Sanderson J. E., Metreweli C., Celermajer D. S. Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans Circulation 1997 96, N 8: 2542–2544.