THE STUDY OF RS1800629 (G-308А) POLYMORPHISM OF THE TNF GENE IN PATIENTS WITH MYOCARDIAL INFARCTION WITH ELEVATED ST SEGMENT

Aim. To study the clinical and predictive importance of polymorphism of rs1800629 (G-308A) of TNF gene in patients with STEMI.
Material and methods. Research included patients (171 persons with STEMI), hospitalized to the Kemerovo cardiological center and 188 individuals without the diagnosed cardiovascular diseases. In all patients the genotype had the polymorphism of rs1800629 of TNF gene. Investigation was carried out with help the original DNA microarray.
Results. Associations of the rs1800629 (G-308A) polymorphic variant in the TNF gene with the concentration of the tumor necrosis factor alpha (TNFa) in the blood serum and cardiovascular complications in patients with myocardial infarction with the elevated ST segment (MIST) have been studied. Allele A rs1800629 frequency in patients with MIST (n=171) was 11,7% which did not differ from the frequency in healthy controls (n=188) – 12,2%. Allele A careerstatus was associated with the higher levels of the TNFa concentration in the blood serum measured at the day 10th-14th after MI: 11,02 pg/ml compared to 9,49 in G homozygotes (p=0,045). While analyzing the clinical status of MIpatients after one year follow up, it was revealed that A allele has the frequency 19% in patients with progressive angina pectoris (AP) compared to 10% in  patients without progressive AP, and 16% in patients with cardiovascula rcomplications (CVC) such as repeated MI, stroke, instable AP or death from cardiovascular reasons compared to 9% frequency in patients without CVC, which was not statistically significant. We had shown in earlier s tudy that TNFa high level in patients with MI is related to the risk of CVC. Although, in current study we did not detect an association of the rs1800629 with progression of the AP, chronic heart failure decompensation, CVC or death from cardiovascularreasons in one year after IM. Thus, rs1800629 allele A does influence TNFa concentrations, but there is no data supporting the fact that this variant is an independent risk factor for IM and its complications.

Conclusion. The results indicate possible predictive value of rs1800629 polymorphism of TNF gene to predict the cardiovascular events in patients with STEMI during 12 months of follow up.

1. Golubenko MV, Stepanov VA, Makeeva OA, et al. The DNA-micro array for research of structure of hereditary predisposition to cardiovascular diseases. In: Molecular and biological technologies in medical practice. Novosibirsk: Alpha Vista Н. 2009; 13:42-9. Russian (Голубенко М. В., Степанов В. А., Макеева О. А. и др. ДНК-чип для исследования структуры наследственной предрасположенности к сердечно-сосудистым заболеваниям В кн: Молекулярно-биологические технологии в медицинской практике. Новосибирск: Альфа Виста Н.; 2009. Вып. 13: 42-9).

2. Zheng MH, Xiao DD, Lin XF, et al. The tumour necrosis factor-a-238A allele increases the risk of chronic HBV infection in. European populations. J Viral Hepat 2012; 19(2):11-7.

3. Liu Z,Ding Y, Xiu L, et al. A meta-analysis of the association between TNF-a -308G>A polymorphism and type 2 diabetes mellitus in Han Chinese population. PLoS One 2013; 8(3): 59421.

4. Zhu H, Zhang Z, Lei X, et al. Tumor necrosis factor alpha -308G>A, -863C>A, - 857C> Tgene polymorphisms and tuberculosis susceptibility: a meta-analysis. Gene 2012; 10(2): 206-14.

5. Wang J, Jin X, Wang H, et al. The -308G/A Polymorphism of the Tumor Necrosis Factoralpha Gene Is Associated with the Risk of Upper Aerodigestive Tract Cancer: A Metaanalysis. Tohoku J Exp Med 2013; 229(4): 245-54.

6. Granja AG, Nogal ML, Hurtado C, et al. The Viral Protein A238L Inhibits TNF-_ Expression through a CBP/p300 Transcriptional Coactivators Pathway1. The Journal of Immunology 2006; 176: 451-62.

7. Shevchenko AV, Golovanova OV, Konenkov VI. Features of polymorphism of promotor regions of genes cytokines IL1, IL4, IL5, IL6, IL10 and TNFa at the European population of Western Siberia. Immunology 2010; 4: 176-81. Russian (Шевченко А. В., Голованова О. В., Коненков В. И. Особенности полиморфизма промоторных регионов генов цитокинов IL1, IL4, IL5, IL6, IL10 и TNFa у европеоидного населения Западной Сибири. Иммунология 2010; 4: 176-81).

8. Konenkov VI, Shevchenko AV, Prokofiev VF, et al. Polymorphism of genes of proteinsregulators of an inflammation at the atherosclerosis complicated by development of an acute myocardial infarction. Atherosclerosis 2011; 7(1):5-18. Russian (Коненков В. И., Шевченко А. В., Прокофьев В. Ф. и др. Полиморфизм генов белков-регуляторов воспаления при атеросклерозе, осложненном развитием острого инфаркта миокарда. Атеросклероз 2011; 7(1): 5-18.).

9. Elahi MM, Gilmour A, Matata BM, et al. A variant of position -308 of the Tumour necrosis factor alpha gene promoter and the risk of coronary heart disease. Heart Lung Circ. 2008; 17(1): 14-8.

10. Wang XL, Oosterhof J. Tumour necrosis factor alpha G-308-A polymorphism and risk for coronary artery disease. Clin Sci. 2000; 98:435-7.

11. Padovani JC, Pazin-Filho A, Simoes MV, et al. Gene Polymorphisms in the TNF locus and the Risk of Myocardial Infarction. Thrombosis Research. 2000; 100: 263-9.

12. Wilson AG, Symons JA, McDowell TL, et al. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc. Natl. Acad. Sci. USA 1997; 94: 3195.

13. Zykov MV, Kashtalap VV, Zykova DS, et al. Predicting of myocardial infarction complications within one-wear follow-up. Siberian medical journal 2011; 26(4), 1:41-6. Russian (Зыков М.В., Кашталап В.В., Зыкова Д.С.и др.) Прогнозирование осложнений инфаркта миокарда в течение одного года наблюдения. Сибирский медицинский журнал 2011; 26(4), 1: 41-6).

14. Szabó GV, Acsády Gy. Tumornecrosis-factor-a 308 GA Polymorphism in atherosclerotic patients. Pathol. Oncol. Res. 2011; 17(4): 853-7.

15. Barbarash OL, Kashtalap VV. Diagnosis of latent forms of non-coronary atherosclerosis in acute coronary syndrome patients. Is there any practical sense? Complex problems of cardiovascular diseases 2012; 1: 12-6. Russian (Барбараш О. Л., Кашталап В. В. Выявление латентного некоронарного атеросклероза у пациентов с острым коронарным синдромом. Есть ли смысл? Комплексные проблемы сердечно-сосудистых заболеваний 2012;1:12-6).