PLATELET AGGREGATION ACTIVITY AND CARRIERSHIP OF ALLELIC VARIANTS IN GENES OF PLATELET GLYCOPROTEIN RECEPTORS IN PATIENTS WITH CONGENITAL HEART DISEASES WITH SINGLE VENTRICLE DEFECTS

Aim: The aim of the study was to analyze the results of genetic testing of platelet glycoprotein receptors and their aggregation activity in patients with congenital heart diseases (CHD) with single ventricle defect (SVD). The study comprised 50 children referred for planned surgical correction of CHD. In all patients, the value of platelet aggregation activity was assessed in the presence of Cardiomagnyl and was compared with the results of genetic testing of platelet receptors for collagen ITGA2:807С>Т and for fibrinogen ITGB3:1565T>C. In study patients, the average levels of platelet aggregation in the presence of collagen inductor were 52.5% in carriers of СС genotype of ITGA2:807 gene, 49.0% in carriers of СT genotype, and 65.1% in children carrying TT genotype. The average levels of platelet aggregation in the presence of epinephrine-inductor were 56.3% and 65.8% in carriers of ТТ and ТС genotypes, respectivley, and did not significantly differ from aggregation I patients with CC genotype: 75.6% (р=0.506). In group of study patients with CHD, no relationships of allelic variants of platelet glycoprotein receptor genes for collagen ITGA2:807С>Т and for fibrinogen ITGB3:1565T>C with platelet aggregation activity level were found. Meanwhile, the absence of changes in platelet aggregation activity in response to collagen and epinephrine was found in 30% and 38% of children with CHD administered with Cardiomagnyl.

агрегационная активность тромбоцитов, полиморфизм генов, гликопротеиновые рецепторы тромбоцитов, врожденный порок сердца, дети, platelet aggregation activity, genetic polymorphism, platelet glycoprotein receptors, congenital heart disease, children

1. Львова О.А. Генетически детерминированные нарушения гемокоагуляции как причина ишемических инсультов у детей // Журнал неврологии и психиатрии. Инсульт. - 2011. - № 12. - С. 3-9.

2. Макацария А.Д., Бицадзе В.О. Тромбофилии и противотромботическая терапия в акушерской практике. - М. : Триада-Х, 2003. - 903 с.

3. Окороков А.Н. Диагностика болезней внутренних органов. - М. : Медицинская литература, 2002. - Т. 5. - 489 с.

4. Скоромец А.А., Тадтаева З.Г., Па Т.Е., Скоромец А.П. Генетические признаки тромбофилии при инсульте у детей и подростков // Вестн. С.-Петерб. ун-та. - 2011. - № 4. - С. 62-68.

5. Чугунова О.Л., М.В. Шумихина, Н.Л. Козловская, А.И. Гуревич Функциональное состояние почек и почечной гемодинамики у детей с наследственной тромбофилией // Нефрология и диализ. - 2012. - Т. 14, № 4. - С. 224-235.

6. Airan B., Sharma R., Chowdhury U.K. et al. Univentricular repair: is routine fenestration justified? // Ann. Thorac. Surg. - 2000. - Vol. 69. - P. 1900-1906.

7. Azakie A., McCrindle B.W., Arsdell G.V. et al. Extracardiac versus lateral tunnel cavopulmonary connections at a single institution: impact on outcomes // J. Thorac. Cardiovasc. Surg. - 2000. - Vol. 122. - P. 1219-1228.

8. Beckerath N. Glycoprotein Ia gene C807T polymorphism and risk for major adverse cardiac events within the first 30 days after coronary artery stenting // Blood. - 2000. - Vol. 95, No. 11. - P. 3297-3301.

9. Bennett J.S., Catella-Lawson F., Rut A.R. et al. Effect of the PlA2 alloantigen on the function of b3-integrins in platelets. Blood. - 2001. - Vol. 97, No. 10. - P. 3093-3099.

10. Bussel J.B. Platelets: New understanding of platelet glycoproteins and their role in disease // Hematology (Am. Soc. Hematol. Educ. Program). - 2000. - P. 222-240.

11. Corral J. Role of the 807 C/T polymorphism of the a 2 gene in platelet GP IA collagen receptor expression and function effect in thromboembolic diseases // Thromb. Haemost. - 1999. - Vol. 81, No. 6. - P. 951-956.

12. Feinbloom D. Assessment of hemostatic risk factors in predicting arterial thrombotic events // Arteriosclerosis, Thrombosis and Vascular Biology. - 2005. - Vol. 25. - P. 2043-2053.

13. Herrmann S. The Leu33/Pro polymorphism (PlA1/PlA2) of the glycoprotein IIIa (GPIIIa) receptor is not related to myocardial infarction in the ECTIM Study. Etude Cas-Temoins de l’Infarctus du Myocarde // Thromb. Haemost. - 1997. - Vol. 77. - P. 1179-1181.

14. Hooper W.C. The relationship between polymorphisms in the endothelial cell nitric oxide synthase gene and the platelet GPIIIa gene with myocardial infarction and venous thromboembolism in African Americans // Chest. - 1999. - Vol. 116. - P. 880-886.

15. Kastrati A. PlA Polymorphism of platelet glycoprotein IIIa and risk of restenosis after coronary stent placement // Circulation. - 1999. - Vol. 99. - P. 1005-1010.

16. Kunicki T. Variability of integrin alpha 2beta 1 activity on human platelets // Blood. - 1993. - Vol. 82. - P. 2693-2703.

17. Lane D.A. Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease // Blood. - 2000. - Vol. 95, No. 5. - P. 1517-1532.

18. Newman P.J. 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.

19. O’Donnell C.J., Larson M.G., Feng D. et al. Genetic and environmental contributions to platelet aggregation: the Framingham Heart Study // Circulation. - 2001. - Vol. 103, No. 35. - P. 3051-3056.

20. Quinn M.J., Topol E.J. Common variations in platelet glycoproteins: harmacogenomic implications // Pharmacogenomics. - 2001. - Vol. 2, No. 4. - P. 341-352.

21. Ridker P. PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous // Lancet. - 1997. - Vol. 349 - P. 385-388.

22. Santoso S. Association of the platelet glycoprotein ia c807t gene polymorphism with nonfatal myocardial infarction in younger patients // Blood. - 1999. - Vol. 93, No. 8 - P. 2449-2453.

23. Szczeklik F. Reasons for resistance to aspirin in cardiovascular disease // Circulation. - 2002. - Vol. 106. - P. 181-182.