mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2009-6-557-566mimmun-367Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESАНАЛИЗ ВЗАИМОСВЯЗИ ПОЛИМОРФИЗМА ГЕНА IL6 (-174 G/C) И КЛАССИЧЕСКИХ ФАКТОРОВ РИСКА У ПАЦИЕНТОВ С ОСТРЫМ ИНФАРКТОМ МИОКАРДА В АНАМНЕЗЕANALYSIS OF CORRELATION BETWEEN IL 6 GENE POLYMORPHISM (-174 G /C) AND CLASSIC RISK FACTORS IN PATIENTS WITH PREVIOUS MYOCARDIAL INFARCTIONSШевченкоА. В.ShevchenkoA. V.

630117, ул. Академика Тимакова, 2. Тел.: (383) 227-01-94. Факс: (383) 227-01-96

shalla64@mail.ruГоловановаО. В.GolovanovaO. V.shalla64@mail.ruКоненковВ. И.KonenkovV. I.shalla64@mail.ruВоеводаМ. И.VoevodaM. I.shalla64@mail.ruМаксимовВ. Н.MaximovV. N.shalla64@mail.ruТолкачеваО. М.TolkachevaO. M.shalla64@mail.ruНИИ клинической и экспериментальной лимфологии СО РАМН, г. НовосибирскRussian FederationНИИ терапии СО РАМН, г. НовосибирскRussian FederationМУЗ Городская клиническая больница № 29, г. НовокузнецкRussian Federation200920072014116557566Copyright © Шевченко А.В., Голованова О.В., Коненков В.И., Воевода М.И., Максимов В.Н., Толкачева О.М., 20142014Шевченко А.В., Голованова О.В., Коненков В.И., Воевода М.И., Максимов В.Н., Толкачева О.М.Shevchenko A.V., Golovanova O.V., Konenkov V.I., Voevoda M.I., Maximov V.N., Tolkacheva O.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/367

Резюме. Мы провели анализ ассоциированности промоторного региона гена IL6 (-174 G/C) с классическими факторами риска ССЗ у мужчин, проживающих в западносибирском регионе с инфарктом миокарда (ИМ) в анамнезе. Нами выявлено снижение частоты IL6*-174 GG генотипа в группе с ИМ в анамнезе относительно здоровых. Частота этого же генотипа снижена и при анализе курящих пациентов относительно некурящих здоровых. С другой стороны, выявлено увеличение индекса массы тела и артериального давления у пациентов с IL6*-174 G в генотипе относительно здоровых. Следовательно, анализируемый полиморфизм промоторного региона гена IL6 можно рассматривать как дополнительный конституциональный фактор предрасположенности к развитию сосудистых повреждений.

Abstract. We have carried out a prevalence analysis of IL6 (-174 G/C) gene promoter polymorphism and traditional cardiovascular risk factors in male patients living in the West Siberia that survived myocardial infarction (MI) in their anamnesis. Analysis of genotype frequencies have shown decrease of *-174 GG genotype in the patients with MI. Frequency of the same genotype is decreased among smoking patients as compared to healthy non-smokers. On other hand, an increased body weight and arterial pressure indexes increase is found in IL6*-174 G patients, versus healthy population. Hence, the analyzed IL6 (-174 G/C) polymorphism may be considered as an additional predisposition factor for development of vascular damage.

инфаркт миокардаполиморфизм IL-6классические факторы риска ИМmyocardial infarctionpolymorphism IL-6cardiovascular risk factorsReferencesБогова О.Т., Чукаева И.И. Инфаркт миокарда. Воспаление и прогноз // Российский кардиологический журнал.– 2003. – № 4. – С. 18 - 23.Богова О.Т., Чукаева И.И. Инфаркт миокарда. Воспаление и прогноз // Российский кардиологический журнал.– 2003. – № 4. – С. 18 - 23.Доценко Э.А., Юпатов Г.И., Чиркин А.А. Холестерин и липопротеины низкой плотности как эндогенные иммуномодуляторы // Иммунопатология, аллергология, инфектология. – 2001. – № 3. – С. 6-15.Доценко Э.А., Юпатов Г.И., Чиркин А.А. Холестерин и липопротеины низкой плотности как эндогенные иммуномодуляторы // Иммунопатология, аллергология, инфектология. – 2001. – № 3. – С. 6-15.Лутай М.И. Атеросклероз: современный взгляд на патогенез. – http: //www.rql.kiev.ua/cardio_j/2004/1/lutay.htm.Лутай М.И. Атеросклероз: современный взгляд на патогенез. – http: //www.rql.kiev.ua/cardio_j/2004/1/lutay.htm.Школьник В.В. Динамика уровня интерлейкина-6 у больных с острым инфарктом миокарда при лечении ингибиторами ангиотензинпревращающего фермента // Украинський терапевтичний журнал. – 2004. – № 1. – С. 74 - 76.Школьник В.В. Динамика уровня интерлейкина-6 у больных с острым инфарктом миокарда при лечении ингибиторами ангиотензинпревращающего фермента // Украинський терапевтичний журнал. – 2004. – № 1. – С. 74 - 76.Basso F., Lowe G.D.O., Rumley A., McMahon A.D., Humphries S.E. Interleukin-6-174 G > C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS), on behalf of the WOSCOPS Group // Arterioscler Thromb. Vasc. Biol. – 2002. – Vol. 22. – P. 599-604.Basso F., Lowe G.D.O., Rumley A., McMahon A.D., Humphries S.E. Interleukin-6-174 G > C Polymorphism and Risk of Coronary Heart Disease in West of Scotland Coronary Prevention Study (WOSCOPS), on behalf of the WOSCOPS Group // Arterioscler Thromb. Vasc. Biol. – 2002. – Vol. 22. – P. 599-604.Bennermo M., Held C., Stemme S., Ericsson C.-G., Silveira A., Green F., Tornvall P. Genetic Predisposition of the Interleukin-6 Response to Inflammation: Implications for a Variety of Major Diseases? // Clinical Chemistry. – 2004. – Vol. 50, – N 11. – P. 2136-2140.Bennermo M., Held C., Stemme S., Ericsson C.-G., Silveira A., Green F., Tornvall P. Genetic Predisposition of the Interleukin-6 Response to Inflammation: Implications for a Variety of Major Diseases? // Clinical Chemistry. – 2004. – Vol. 50, – N 11. – P. 2136-2140.Bland J. M., Altman D.G., Education and debate. The odds ratio // BMJ. – 2000. – Vol. 320. – P. 1468.Bland J. M., Altman D.G., Education and debate. The odds ratio // BMJ. – 2000. – Vol. 320. – P. 1468.Brull D.J., Montgomery H.E., Sanders J., Dhamrait S., Luong L., Rumley A., Lowe G.D.O., Humphries S.E. Atherosclerosis and Lipoproteins Interleukin-6 Gene -174 G > C and -572 G > C Promoter Polymorphisms Are Strong Predictors of Plasma Interleukin-6 Levels After Coronary Artery Bypass Surgery // Arterioscler Thromb Vasc Biol.- 2001. – Vol. 21. – P. 1458-1463.Brull D.J., Montgomery H.E., Sanders J., Dhamrait S., Luong L., Rumley A., Lowe G.D.O., Humphries S.E. Atherosclerosis and Lipoproteins Interleukin-6 Gene -174 G > C and -572 G > C Promoter Polymorphisms Are Strong Predictors of Plasma Interleukin-6 Levels After Coronary Artery Bypass Surgery // Arterioscler Thromb Vasc Biol.- 2001. – Vol. 21. – P. 1458-1463.Crea F., Biasucci L.M., Buffon A., Liuzzo G., Monaco C., Caligiuri G., Kol A., Sperti G., Cianflone D., Maseri A. Role of inflammation in the pathogenesis of unstable coronary artery disease // Am. J. Cardiol. – 1997. – Vol. 80. – P. 10-16.Crea F., Biasucci L.M., Buffon A., Liuzzo G., Monaco C., Caligiuri G., Kol A., Sperti G., Cianflone D., Maseri A. Role of inflammation in the pathogenesis of unstable coronary artery disease // Am. J. Cardiol. – 1997. – Vol. 80. – P. 10-16.Fernandez-Real J.-M., Broch M., Vendrell J., Bal Richart C., Ricart W. Interleukin-6 gene polymorphism and lipid abnormalities in healthy Subjects // J. Clin. Endocrinol. Metab. – 2000. – Vol. 85. – P. 1334-1339.Fernandez-Real J.-M., Broch M., Vendrell J., Bal Richart C., Ricart W. Interleukin-6 gene polymorphism and lipid abnormalities in healthy Subjects // J. Clin. Endocrinol. Metab. – 2000. – Vol. 85. – P. 1334-1339.Fernandez-Real J.-M., Vendrell J.n, Richart C., Gutierrez C., Ricart W. Platelet count and Interleukin 6 Gene polymorphism in healthy subjects // BMC Medical Genetics. – 2001. – Vol. 2, N 6. – P. 1471 - 2350.Fernandez-Real J.-M., Vendrell J.n, Richart C., Gutierrez C., Ricart W. Platelet count and Interleukin 6 Gene polymorphism in healthy subjects // BMC Medical Genetics. – 2001. – Vol. 2, N 6. – P. 1471 - 2350.Freeman D.J., Griffin B.A., Murray E. Smoking and plasma lipoproteins in man: effects on low density lipoprotein cholesterol levels and high density lipoprotein subfraction distribution // Eur. J. Clin. Invest. – 1993. – Vol. 23. – P. 630-640.Freeman D.J., Griffin B.A., Murray E. Smoking and plasma lipoproteins in man: effects on low density lipoprotein cholesterol levels and high density lipoprotein subfraction distribution // Eur. J. Clin. Invest. – 1993. – Vol. 23. – P. 630-640.Gabriel A,S., Ahnve S., Wretlind B., Martinsson A. IL-6 and IL-1 receptor antagonist in stable angina pectoris and relation of IL-6 to clinical findings in acute myocardial infarction //J. Intern. Med. – 2000. – Vol. 248. – P. 61-66.Gabriel A,S., Ahnve S., Wretlind B., Martinsson A. IL-6 and IL-1 receptor antagonist in stable angina pectoris and relation of IL-6 to clinical findings in acute myocardial infarction //J. Intern. Med. – 2000. – Vol. 248. – P. 61-66.Cardellini M., Perego L., D’Adamo M., Marini M.A., Procopio C., Hribal M.L., Andreozzi F., Frontoni S., Giacomelli M., Paganelli M., Pontiroli A.E., Lauro R., Folli F., Sesti G. C -174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance // Diabetes Care. – 2005. – Vol. 28. – P. 2007-2012.Cardellini M., Perego L., D’Adamo M., Marini M.A., Procopio C., Hribal M.L., Andreozzi F., Frontoni S., Giacomelli M., Paganelli M., Pontiroli A.E., Lauro R., Folli F., Sesti G. C -174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance // Diabetes Care. – 2005. – Vol. 28. – P. 2007-2012.Georges J.-L., Loukaci V., Poirier O., Evans A.L.G., Ruidavets D.A.J.-B., Cambien F., Tiret L. Interleukin-6 gene polymorphisms and susceptibility to myocardial infarction: the ECTIM study // J. Mol. Med. – 2001. – Vol. 79. – P. 300- 305.Georges J.-L., Loukaci V., Poirier O., Evans A.L.G., Ruidavets D.A.J.-B., Cambien F., Tiret L. Interleukin-6 gene polymorphisms and susceptibility to myocardial infarction: the ECTIM study // J. Mol. Med. – 2001. – Vol. 79. – P. 300- 305.Goyenechea E., Parra D., Martínez J.A. Role of IL-6 and its-174 G > C polymorphism in weight management and in the metabolic comorbidities associated with obesity // An Sist. Sanit. Navar. – 2005. – Vol. 28, N 3. – P. 357-366.Goyenechea E., Parra D., Martínez J.A. Role of IL-6 and its-174 G > C polymorphism in weight management and in the metabolic comorbidities associated with obesity // An Sist. Sanit. Navar. – 2005. – Vol. 28, N 3. – P. 357-366.Goyenechea E., Parra D., Martínez J.A. Impact of interleukin 6-174 G > C polymorphism on obesity-related metabolic disorders in people with excess in body weight // Metabolism. – 2007. – Vol. 56, N 12. – P. 1643-1648.Goyenechea E., Parra D., Martínez J.A. Impact of interleukin 6-174 G > C polymorphism on obesity-related metabolic disorders in people with excess in body weight // Metabolism. – 2007. – Vol. 56, N 12. – P. 1643-1648.Henningsson S., Håkansson A., Westberg L., Baghaei F., Rosmond R., Holm G., Ekman A., Nissbrandt H., Eriksson E. Interleukin-6 Gene Polymorphism -174 G/C Influences Plasma Lipid Levels in Women // OBESITY. – 2006. – Vol. 14, N 11. – P. 1868-1873.Henningsson S., Håkansson A., Westberg L., Baghaei F., Rosmond R., Holm G., Ekman A., Nissbrandt H., Eriksson E. Interleukin-6 Gene Polymorphism -174 G/C Influences Plasma Lipid Levels in Women // OBESITY. – 2006. – Vol. 14, N 11. – P. 1868-1873.Humphries1 S.E., Luong1 L.A., Ogg1 M.S., Hawe1 E., Miller G.J. The interleukin-6 - 174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men // European Heart Journal. – 2001. – Vol. 22. – P. 2243-2252.Humphries1 S.E., Luong1 L.A., Ogg1 M.S., Hawe1 E., Miller G.J. The interleukin-6 - 174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men // European Heart Journal. – 2001. – Vol. 22. – P. 2243-2252.Jones K.G., Brull D.J., Brown L.C., Greenhalgh R.M., Humphries S.E., Powell J.T. Interleukin-6 (IL-6) and the Prognosis of Abdominal Aortic Aneurysms // Circulation. – 2001. – Vol. 103. – P. 2260-2265.Jones K.G., Brull D.J., Brown L.C., Greenhalgh R.M., Humphries S.E., Powell J.T. Interleukin-6 (IL-6) and the Prognosis of Abdominal Aortic Aneurysms // Circulation. – 2001. – Vol. 103. – P. 2260-2265.Lieb W., Pavlik R., Erdmann J., Mayer B.,Holmer S.R., Fischer M., Baessler A., Hengstenberg C., Loewel H., Doering A., Riegger G.A., Schunkert H. No association of interleukin-6 gene polymorphism (-174 G/C) with myocardial infarction or traditional cardiovascular risk factors // Int. J. Cardiol. – 2004. – Vol. 97, N 2. – P. 205-212.Lieb W., Pavlik R., Erdmann J., Mayer B.,Holmer S.R., Fischer M., Baessler A., Hengstenberg C., Loewel H., Doering A., Riegger G.A., Schunkert H. No association of interleukin-6 gene polymorphism (-174 G/C) with myocardial infarction or traditional cardiovascular risk factors // Int. J. Cardiol. – 2004. – Vol. 97, N 2. – P. 205-212.Lowe G.D.O., Rumley A. Coagulation, fibrinolysis and cardiovascular disease // Fibrinolysis & Proteolysis. – 1999. – Vol. 13. – P. 91-98.Lowe G.D.O., Rumley A. Coagulation, fibrinolysis and cardiovascular disease // Fibrinolysis & Proteolysis. – 1999. – Vol. 13. – P. 91-98.Lusis A.J., Fogelman A.M., Fonarow G.C. Genetic basis of atherosclerosis. II. Clinical implications // Circulation. – 2004. – Vol. 110. – P. 2066-2071.Lusis A.J., Fogelman A.M., Fonarow G.C. Genetic basis of atherosclerosis. II. Clinical implications // Circulation. – 2004. – Vol. 110. – P. 2066-2071.Ridker P.M., Rifai N., Stampfer M.J., Hennekens C.H. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men // Circulation. – 2000. – Vol. 101. – P. 1767-1772.Ridker P.M., Rifai N., Stampfer M.J., Hennekens C.H. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men // Circulation. – 2000. – Vol. 101. – P. 1767-1772.Seed M., Humphries S.E., Ayres K.L., Miller G.J. Lipoprotein (a) as a predictor for myocardial infarction in the Second Northwick Park Heart Study — a prospective study in middle-aged men //Am. J. Med. – 2001. – Vol. 110. – P. 22-27.Seed M., Humphries S.E., Ayres K.L., Miller G.J. Lipoprotein (a) as a predictor for myocardial infarction in the Second Northwick Park Heart Study — a prospective study in middle-aged men //Am. J. Med. – 2001. – Vol. 110. – P. 22-27.Signorelli S.S., Mazzarino M.C., Di Pino L. High circulating levels of cytokines (IL-6 and TNFalpha), adhesion molecules (VCAM-1 and ICAM-1) and selectins in patients with peripheral arterial disease at rest and after a treadmill test // Vasc. Med. – 2003. – Vol. 8. – P. 15-19.Signorelli S.S., Mazzarino M.C., Di Pino L. High circulating levels of cytokines (IL-6 and TNFalpha), adhesion molecules (VCAM-1 and ICAM-1) and selectins in patients with peripheral arterial disease at rest and after a treadmill test // Vasc. Med. – 2003. – Vol. 8. – P. 15-19.Takano M., Itoh N., Yayama K., Yamano M., Ohtani R.,Okamoto H. Interleukin-6 as a mediator responsible for inflammation-induced increase in plasma angiotensinogen // Biochem. Pharmacol. – 2000. – Vol. 45. – P. 201-206.Takano M., Itoh N., Yayama K., Yamano M., Ohtani R.,Okamoto H. Interleukin-6 as a mediator responsible for inflammation-induced increase in plasma angiotensinogen // Biochem. Pharmacol. – 2000. – Vol. 45. – P. 201-206.Tretjakovs P., Latkovskis G., Licis N., Juhnevica D., Jurka A., Bormane I., Aivars J.I., Stifts A., Pirags V. Lnterleukin-6 gene promoter -174 G/C polymorphism and insulin resistance: a pilot study // Clinical chemistry and laboratory medicine. – 2007. – Vol. 45, N 9. – P. 1145-1148.Tretjakovs P., Latkovskis G., Licis N., Juhnevica D., Jurka A., Bormane I., Aivars J.I., Stifts A., Pirags V. Lnterleukin-6 gene promoter -174 G/C polymorphism and insulin resistance: a pilot study // Clinical chemistry and laboratory medicine. – 2007. – Vol. 45, N 9. – P. 1145-1148.Verheye S., De Meyer R.Y., Langenhove G.V. In vivo temperature heterogeneity of atherosclerotic plaques is determined by plaque composition // Circulation. – 2002. – Vol. 105, N 13. – P. 1596 - 1601.Verheye S., De Meyer R.Y., Langenhove G.V. In vivo temperature heterogeneity of atherosclerotic plaques is determined by plaque composition // Circulation. – 2002. – Vol. 105, N 13. – P. 1596 - 1601.Woodward M., Rumley A., Tunstall-Pedoe H., Lowe G.D.O. Associations of blood rheology and interleukin-6 with cardiovascularrisk factors and prevalent cardiovascular disease // Br. J. Haematology. – 1999. – Vol. 104. – P. 246-257.Woodward M., Rumley A., Tunstall-Pedoe H., Lowe G.D.O. Associations of blood rheology and interleukin-6 with cardiovascularrisk factors and prevalent cardiovascular disease // Br. J. Haematology. – 1999. – Vol. 104. – P. 246-257.Xenophontos S., Hadjivassiliou M., Karagrigoriou A., Demetriou N., Miltiadous G., Marcou I., Elisaf M., Mikhailidis D.P., Cariolou M.A. Low HDL Cholesterol, Polymorphism are Associated with Myocardial Infarction in Greek Cypriot Males. A Pilot Study // The Open Cardiovascular Medicine Journal. – 2008. – Vol. 2. – P. 52-59.Xenophontos S., Hadjivassiliou M., Karagrigoriou A., Demetriou N., Miltiadous G., Marcou I., Elisaf M., Mikhailidis D.P., Cariolou M.A. Low HDL Cholesterol, Polymorphism are Associated with Myocardial Infarction in Greek Cypriot Males. A Pilot Study // The Open Cardiovascular Medicine Journal. – 2008. – Vol. 2. – P. 52-59.Yudkin J.S., Stehouwer C.D.A., Emeis J.J. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction – a potential role for cytokines originating from adipose tissue? // Arterioscler. Thromb. Vascular. Biol. – 1999. – Vol. 19. – P. 972 - 978.Yudkin J.S., Stehouwer C.D.A., Emeis J.J. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction – a potential role for cytokines originating from adipose tissue? // Arterioscler. Thromb. Vascular. Biol. – 1999. – Vol. 19. – P. 972 - 978.

The authors declare that there are no conflicts of interest present.