ASSOCIATION OF TNF AND LTA GENES WITH ATHEROSCLEROSIS COMPLICATIONSIN PATIENTS WITH HISTORY OF ACUTE CORONARY SYNDROME

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Abstract


The aim of this study was to investigate an association of polymorphic markers G(-308)A of TNF gene and Thr26Asn of LTA gene with the frequency of poor outcomes in patients with the history of acute coronary syndrome.Methods. A total of 1145 patients admitted to cardiological hospitals of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don with ischemic heart disease exacerbation were examined. The maximum follow up time was 3.2 years. The identification of polymorphic marker allele was carried out by hybridization-fluorescent analysis using real-time polymerase chain reaction.Results. In case of Thr26Asn polymorphic marker of LTA gene we have not found any association with the frequency of poor outcomes in patients with the history of acute coronary syndrome. However, in case of G(-308)A polymorphic marker of TNF gene we have found the reliable association. The carriers of GA and AA genotypes has higher frequency of poor outcomes in comparison with the carriers of GG genotypes. The survival time to the endpoint for carriers of the GA and AA genotypes was 43.3 months (95% CI = 40.04 - 46.56) vs. 49.6 months (95% CI = 47.38 - 51.82) for carriers of theGG genotype (χ2 = 15.4; р < 0.001).The results of our study allow to make a conclusion that the G(-308)A polymorphic marker of TNF gene is significantly associated with hereditary predisposition to unfavourable outcome in patients with history of acute coronary syndrome.

АССОЦИАЦИЯ ГЕНОВ TNF И LTA С ОСЛОЖНЕНИЯМИ АТЕРОСКЛЕРОЗА У БОЛЬНЫХ, ПЕРЕНЕСШИХ ОБОСТРЕНИЕИШЕМИЧЕСКОЙ БОЛЕЗНИ СЕРДЦА

D A Zateyshchikov

Email: dz@bk.ru

A A Pushkov

A G Nikitin

A N Brovkin

M A Evdokimova

T N Baklanova

S N Tereschenko

N A Dzhaiani

E V Akatova

M G Glezer

A S Galyavich

N A Koziolova

A V Yagoda

O I Boyeva

E V Horolets

S V Shlyk

E G Volkova

V O Konstantinov

V V Nosikov

Email: nosikov@genetika.ru

K A Blagodatskih

  1. Оганов Р.Г., Масленникова Г.Я. Вклад сердечно-сосудистых и других неинфекционных заболеваний в здоровье населения России. Сердце. 2003; 2: 58-61.
  2. Шевченко О.П., Мишнев О.Д. Ишемическая болезнь сердца. М.: Реафарм. 2005. 416 с.
  3. Goyal A., Blazing M. Should we measure C-reactive protein levels to ascertain the adequacy of statin therapy in patients who are at very high risk for a coronary heart disease event? Am Heart J. 2005; 150: 650-651.
  4. Аронов Д.А. Первичная и вторичная профилактика сердечно-сосудистых заболеваний – интерполяция на Россию. Сердце. 2002; 3:109-112.
  5. Berliner J.A., Navab M., Fogelman A.M., et al. Atherosclerosis: Basic Mechanisms: Oxidation, Inflammation, and Genetics. Circulation 1995;91 (9): 2488-96.
  6. de Craen A.J., Posthuma D., Remarque E.J., van den Biggelaar A.H., Westendorp R.G., Boomsma D.I. Heritability estimates of innate immunity: an extended twin study. Genes Immun. 2005; 6: 167-170.
  7. Jermendy G., Horváth T., Littvay L., et al. Effect of genetic and environmental influences on cardiometabolic risk factors: a twin study. Cardiovasc Diabetol 2011;10: 96.
  8. Raman K., Chong M., Akhtar-Danesh G.G., et al. Genetic markers of inflammation and their role in cardiovascular disease. Can J Cardiol. 2012; Sep 19 [Epub ahead of print].
  9. Благодатских К.А., Агапкина Ю.В., Никитин А.Г. и соавт. Полиморфные маркеры G(-174)C гена IL6 и G(-1082)A гена IL10 и генетическая предрасположенность к неблагоприятному течению ишемической болезни сердца у больных, перенесших острый коронарный синдром. Молекулярная биология. 2010;44(5): 839-846.
  10. Благодатских К.А., Никитин А.Г., Пушков А.А., и соавт. Полиморфные маркеры G2667C, G3014A, C3872T, A5237G гена CRP и генетическая предрасположенность к неблагоприятному течению ишемической болезни сердца у больных, перенесших обострение ишемической болезни сердца. Медицинская генетика. 2011;4: 3-9.
  11. Carroll M.C., Katzman P., Alicot E.M. et al. Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes. Proc Natl Acad Sci. 1987;84: 8535-9.
  12. Barath P., Fishbein M.C., Cao J., et al. Tumor necrosis factor gene expression in human vascular intimal smooth muscle cells detected by in situ hybridization. Am J Pathol. 1990;137(3): 503-9.
  13. Vaddi K., Nicolini F.A., Mehta P., Mehta J.L. Increased secretion of tumor necrosis factor-alpha and interferon-gamma by mononuclear leukocytes in patients with ischemic heart disease. Relevance in superoxide anion generation. Circulation. 1994; 90 (2): 694-9.
  14. Fernandez-Real J.M., Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev. 2003;24(3):278-301.
  15. Pai J.K., Pischon T., Ma J., Manson J.E., et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med. 2004; 351(25): 2599-2610.
  16. Cesari M., Penninx B.W., Newman A.B., et al. Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation 2003; 8: 2317-22.
  17. Wilson A.G., di Giovine F.S., Blakemore A.I., Duff G.W. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum Mol Genet. 1992;1(5): 353.
  18. Wilson A.G., Symons J.A., McDowell T.L., McDevitt H.O., Duff G.W. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci. 1997; 94(7): 3195-9.
  19. Laxton R., Pearce E., Kyriakou T., Ye S. Association of the lymphotoxin-alpha gene Thr26Asn polymorphism with severity of coronary at herosclerosis. Genes Immun. 2005; 6(6): 539-41.
  20. Mathew C.G. The isolation of high molecular weight eukaryotic DNA. Methods Mol Biol. 1985; 2: 31-4.
  21. R Development Core Team. R: A language and environment for statistical computing. R foundation for Statistical Computing. Vienna, Austria, 2010. Available from www.r-project.org.
  22. Koch W., Tiroch K., von Beckerath N., Schomig A., Kastrati A. Tumor necrosis factor-alpha, lymphotoxin-alpha, and interleukin-10 gene polymorphisms and restenosis after coronary artery stenting. Cytokine. 2003;24(4): 161-171.
  23. Yamada A., Ichihara S., Murase Y., Kato T., et al. Lack of association of polymorphisms of the lymphotoxin alpha gene with myocardial infarction in Japanese. J Mol Med. 2004;82(7): 477-83.
  24. Clarke R., Xu P, Bennett D., Lewington S., et al. Lymphotoxin-alpha gene and risk of myocardial infarction in 6,928 cases and 2,712 controls in the ISIS case-control study. PLoS Genet. 2006;2(7): e107.
  25. Zhang H.F., Xie S.L., Wang J.F., Chen Y.X., Wang Y., Huang T.C.Tumor necrosis factor-alpha G-308A gene polymorphism and coronary heart disease susceptibility: an updated meta-analysis. Thromb Res. 2011;127(5):400-5.
  26. Plutzky J. Inflammatory pathways in atherosclerosis and acute coronary syndromes. Am J Cardiol. 2001;88(8A):10K-15K.
  27. Allen RD. Polymorphism of the human TNF-alpha promoter – random variation or functional diversity? Mol Immunol. 1999; 36(15-16): 1017-27.

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Copyright (c) 2013 Zateyshchikov D.A., Pushkov A.A., Nikitin A.G., Brovkin A.N., Evdokimova M.A., Baklanova T.N., Tereschenko S.N., Dzhaiani N.A., Akatova E.V., Glezer M.G., Galyavich A.S., Koziolova N.A., Yagoda A.V., Boyeva O.I., Horolets E.V., Shlyk S.V., Volkova E.G., Konstantinov V.O., Nosikov V.V., Blagodatskih K.A.

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