Genetic defects of the coagulation cascade and homocysteine metabolism in the development of cerebral thrombosis

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Abstract

The main goal of the present study was to evaluate the genetic impact of some genes operating in coag­ulation system in the development of the inherited predisposition to ischemic stroke (IS) in men and women before 45 year old. For this purpose we investigated the allele distribution of the 7 following genes - F V Leiden, F2 G20210A, G/A-455 FGB, GP Illa PIA1/A2, A1/A2 5’F7, 4G/5G PAI-1, C677T MTHFR. The plasma level of total homocysteine was analyzed too. The significant prevalence of T 677 MTHFR frequency in the patients with IS compared with controls was found (33% and 27%, respectively, p=0.03). The T 677 allele was associated with high plasma level of total homocysteine. The significant decrease of protective A2 5’F7 allele frequency in IS patients compared with controls was found also (9% and 13%, respectively, p=0.04). The gene-gene interaction between CT or TT genotypes of MTHFR gene and A1A1 genotype of F7 in IS group was showed (OR=1.9 Cl 95% 1.4-2.6). The allele frequencies of other investigated genes were not dif­ferent in patients and control group. These results allowed us to make a conclusion that the inherited predis­position to IS depends on mutations in MTHFR and factor VII genes.

About the authors

O. V. Sirotkina

Konstantinov Institute of Nuclear Physics RAS

Author for correspondence.
Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg, Gatchina

Yu. V. Cherkas

Research Institute of Experimental Medicine of the Russian Academy of Medical Sciences

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

A. V. Merkulova

St. Peterburg Pediatric Medical Academy of the Health Care Ministry RF

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

A. P. Elchaninov

Central Medical-Sanitary Division P122 of the St. Petersburg Research Institute of Experimental Medicine of the Russian Academy of Medical Sciences

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

M. L. Chuhlovina

St. Peterburg Pediatric Medical Academy of the Health Care Ministry RF

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

A. D. Denisenko

Research Institute of Experimental Medicine of the Russian Academy of Medical Sciences

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

I. E. Shvarts

Federal Management of Medico-Biological and Emergency Issues HCM RF, Pavlov State Medical University HCM RF

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

References

  1. Баркаган 3. С. Клинико-патогенетические варианты, номенклатура и основы диагностики гематогенных тромбофилий // Проблемы гематологии. 1996. № 3. С. 5-15.
  2. Давиденкова Е. Ф., Колосова Н. Н., Муравьева 3. М. Наследственные факторы в развитии церебральных инсультов. Л.: Медицина, 1976.
  3. Скоромец А. А. Изменения сердечно-сосудистой системы и мозговые инсульты // Врачебные ведомости. 1997. № 16. С. 45-48.
  4. Харрингтон С., Макги Дж. Молекулярная клиническая диагностика: Методы: Пер. с англ. М.: Мир, 1999.
  5. Черкас Ю. В. Гипергомоцистеинемия как фактор риска развития ишемической болезни сердца: Автореф. дис. ... канд. биол. наук. Санкт-Петербург, 2001.
  6. Bolander-Gouaille С. Focus on Homocysteine and the Vitamins. Involved in its Metabolism. Springer, 2002.
  7. Chambers J. C., Obeid O. A., Kooner J. S. Physiological increments in plasma homocysteine induce vascular endotelial dysfunction in normal human subjects // Arterioscler. Thromb. Vasc. Biol. 2000. Vol. 20. P. 185-188.
  8. Ferraresi P., Marchetti G., Legnani C. et al. The heterozygous 20210 G/A prothrombin genotype is associated with early venous thrombosis in inherited thrombophilias and is not increased in frequency in artery disease // Arterioscler. Thromb. Vasc. Biol. 1997. Vol. 17. P. 2418-2422.
  9. Folsom A. R. Hemostatic risk factors for athero-thrombotic disease: an epidemiologic view // Thromb. Haemost. 2001. Vol. 86. P. 3 66-3 73.
  10. Frosst P., Blom H. J., Milos R., Goyette P. et al. A candidate genetic risk factor for vascular disease: a common mutation in methylentetrahydrofolate reductase // Nature Genet. 1995. Vol. 10. P. 111-113.
  11. Giles W. H., Croft J. B., Greenlund K. J. et al. Total homocyst(e)ine concentration and the likelihood of nonfatal stroke// Stroke. 1998. Vol. 29. P. 2473-2477.
  12. Girelli D., Russo C., Ferraresi C. et al. Polymorphisms in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease// N. Eng. J. Med. 2000. Vol. 343. P. 774-780.
  13. Gudnason V., Stansbie D., Scott J. et al. C677T (thermolabile alanine/valine) polymorphism in methylentetrahydrofolate reductase (MTHFR): its frequency and impact on plasma homocysteine concentration in different European populations // Atherosclerosis. 1998. Vol. 136. P. 347-354.
  14. Gunther G., Junker R., Strater R. et al. Symptomatic ischemic stroke in full-term neonates. Role of acquired and genetic prothrombotic risk factors // Stroke. 2000. Vol. 31. P. 2437-2441.
  15. Hademenos G. J., Alberts M. J., Awad I. et al. Advances in the genetics of cerebrovascular disease and stroke // Neurology. 2001. Vol. 56. P. 997-1008.
  16. Hankey G.J., Eikelboom J. W. Homocysteine and stroke // Curr. Opin. Neurol. 2001. Vol. 14. P. 95-102.
  17. Hassan A., Markus H S. Genetics and ischemic stroke // Brain. 2000. Vol. 123. P. 1784-1812.
  18. Kluijtmans L. A., van den Heuvel L. R, Boers G. H. et al. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease // Am. J. Hum. Genet. 1996. Vol. 58. P. 35-41.
  19. Madonna P., De Stefano V., Coppola A. et al. Hyperhomocysteinemia and other inherited prothrombotic conditions in young adults with a history of ischemic stroke // Stroke. 2002. Vol. 33. P. 51-56.
  20. Malinow M. R. Homocyst(e)ine and arterial occlusive disease // J. Intern. Med. 1994. Vol. 236. P. 603-617.
  21. Mannucci P.M., Mari D., Merati G. et al. Gene polymorphisms predicting high plasma levels of coagulation and fibrinolysis proteins. A study in centenarians // Arterioscler. Thromb. Vasc. Biol.1997. Vol. 17. P. 755-759.
  22. Mansfield M. W., Stickland M. H, Grant P. J. Environmental and genetic factors in relation to elevated circulating levels of plasminogen activator inhibitor-1 in Caucasian patients with noninsulin-dependent diabetes mellitus // Thromb. Haemost. 1995. Vol. 74. P. 842-847.
  23. Marchetti G., Patracchini R., Papacchini M. et al. A polymorphism in the 5’region of coagulation factor VII gene (F7) caused by an inserted decanucleotide // Hum. Genet. 1993. Vol. 90. P. 575-576.
  24. Marcus H. S., Ali N., Swaminathan R. et al. A common polymorphism in the methylentetrahydrofolate reductase gene, homocysteine, and ischemic cerebrovascular disease // Stroke. 1997. Vol. 2 8. P. 1739-1743.
  25. Newman P J., Derbes R. S., Aster R. H. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing // J. Clin. Invest. 1989. Vol. 83. P. 1778-1781.
  26. Nowak-Gottl U., Strater R., Heinecke A. et al. Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood // Blood. 1999. Vol. 94. P. 3 678-3 682.
  27. Ridker R. M., Hennekens С. H, Lindpaintner K. et al. 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. Vol. 332. P. 912-917.
  28. Simmonds R.E., Hermida J., Rezende S.M., Lane D.A. Haemostatic genetic risk factors in arterial thrombosis // Thromb. Haemost. 2001. Vol. 86. P. 374-385.
  29. Tcherkas Y. R, Denisenko A. D. Determination of homocysteine, cysteine and glutamic acid in human plasma by isocratic reversed-phase high-performance liquid chromatography with fluorimetric detection // J. Chromatog. A. 2001. Vol. 913. P. 309-313.
  30. Welch G., Loscalzo J. Homocysteine and atero-thrombosis// N. Engl. J. Med. 1998. Vol. 338. P. 1042-1050.
  31. Yoo J.-H, Chung С.-S., Kang S.-S. Relation of plasma homocyst(e)ine to cerebral infarction and cerebral atherosclerosis // Stroke. 1998. Vol. 29. P. 2478-2483.

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