rpcardioRational Pharmacotherapy in CardiologyРациональная Фармакотерапия в Кардиологии1819-64462225-3653«SILICEA-POLIGRAF» LLC10.20996/1819-6446-2011-7-4-409-425rpcardio-848Research ArticleORIGINAL STUDIESОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯPROTHROMBOTIC POLYMORPHISMS AND LONG-TERM PROGNOSIS OF PATIENTS WITH STABLE ISCHEMIC HEART DISEASEВЛИЯНИЕ ГЕНЕТИЧЕСКИХ ФАКТОРОВ, АССОЦИИРОВАННЫХ С ТРОМБОЗАМИ, НА ДОЛГОСРОЧНЫЙ ПРОГНОЗ БОЛЬНЫХ ХРОНИЧЕСКОЙ ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦАКомаровА. Л.KomarovA. L.

к.м.н., старший научный сотрудник

PhD., MD, Senior research associate

ШахматоваО. О.ShahmatovaO. O.

к.м.н., младший научный сотрудник

PhD, MD, Junior research associate

olga.shahmatova@gmail.comРебриковД. В.RebrikovD. V.

д.б.н., директор по науке НПФ «ДНК-Технология»; руководитель центра коллективного пользования отделения биологических наук РАН «Г енетический полиморфизм» Института общей генетики им. Н. И. Вавилова

PhD, R&D Director of “DNA-T echnology” Research and Production Company; Head of “Genetic Polymorphism” center of General Genetics Institute named after Vavilov N.I.

ТрофимовД. Ю.TrophimovD. Yu.

д.б.н., генеральный директор

PhD, CEO

КоткинаТ. И.KotkinaT. I.

руководитель клинико-диагностической лаборатории

MD, Head of the clinical-diagnostic laboratory

ИлющенкоТ. А.IlyushenkoT. A.

аспирант

MD, Postgraduate student

ДеевА. Д.DeevA. D.

к.физ.-мат.н., руководитель лаборатории биостатистики

PhD, Head of the biostatistics laboratory

ПанченкоЕ. П.PanchenkoE. P.

д.м.н., профессор, руководитель лаборатории клинических проблем атеротромбоза

PhD, MD, Professor , Head of the atherothrombosis clinical problems laboratory

Российский кардиологический научно-производственный комплексРоссияRussian Cardiology Research and Production ComplexRussian FederationНаучно-производственная фирма «ДНК-Технология» Институт общей генетики им. Н.И. ВавиловаРоссия«DNA-Technology» Research and Production Company General Genetics Institute named after N.I. VavilovRussian FederationНаучно-производственная фирма «ДНК-Технология»Россия«DNA-Technology» Research and Production CompanyRussian FederationГосударственный научно-исследовательский центр профилактической медициныРоссияState Research Center for Preventive MedicineRussian Federation20111801201674409425Copyright © Komarov A.L., Shahmatova O.O., Rebrikov D.V., Trophimov D.Y., Kotkina T.I., Ilyushenko T.A., Deev A.D., Panchenko E.P., 20162016Комаров А.Л., Шахматова О.О., Ребриков Д.В., Трофимов Д.Ю., Коткина Т.И., Илющенко Т.А., Деев А.Д., Панченко Е.П.Komarov A.L., Shahmatova O.O., Rebrikov D.V., Trophimov D.Y., Kotkina T.I., Ilyushenko T.A., Deev A.D., Panchenko E.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpcardio.online/jour/article/view/848

Aim. To estimate influence of thrombosis associated genetic factors on cardiovascular complications (CVC) occurrence in patients with stable ischemic heart disease (IHD) on the base of 5-year prospective survey. Material and methods. A total of 503 patients with the mean age of 59.4 years were enrolled into the study. The follow-up period was 5.4 years. Composite endpoint included the following cases of fatal and nonfatal CVC: death, acute coronary syndrome, ischemic stroke/transient ischemic attack, peripheral arterial thrombosis and revascularization of affected vascular system. We determined prevalence and prognostic value of mutations and polymorphisms in genes that encode blood clotting factors (factor V Leiden G1691A, prothrombin G20210A, ß-fibrinogen 455G> A), platelet GPIIIa receptor (C1565T) and enzymes involved in homocysteine metabolism (methylentetrahydrofolate reductase  (C667 T MTHFR) and A1298C, methionine synthase (MTR) A2756G, methionine synthase-reductase (MTRR) A66G and transcobalamin (TCN) C776G). Results. Overall incidence rate of vascular events made up 31.0%. MTHFR and TCN polymorphisms proved to be significant in regard to cardiovascular risk among all studied genetic indices. Carriage of at least C667 T one MTHFR polymorphic allele increased risk of CVC 1.64 times (95% confidence interval (CI) 1.2-2.3, p=0.003). Homozygous carriage of MTHFR 1298 AА and TCN 776 СС “wild” genotypes increased risk of CVC 1.63 times (95% CI 1.2-2.3, р=0.006) and 1.37 times (95% CI 1.001-1.89, р=0.04), respectively. Such genetic variants as MTHFR C667 T/СТ and 1298 AА impacted prognosis only given concomitant decrease in plasma folate level, which was observed in 56.1% of the patients. Conclusion. It can be recommended to test the presence of MTHFR C667 T, MTHFR 1298 AА and TCN 776 СС, and to simultaneously assess folate level in IHD patients in order to clarify risk of unfavorable cardiovascular events.

Цель. На основании результатов пятилетнего проспективного наблюдения определить роль генетических факторов, ассоциированных с тромбозами, в развитии сердечно-сосудистых осложнений (ССО) у больных со стабильной ишемической болезнью сердца (ИБС). Материал и методы. В исследование были включены 503 больных, средний возраст которых составил 59,4 лет. Продолжительность наблюдения — 5,4 года. Комбинированная конечная точка включала случаи фатальных и нефатальных ССО: смерти, острого коронарного синдрома, ишемического инсульта/транзиторной ишемической атаки, периферического артериального тромбоза и реваскуляризации пораженного сосудистого бассейна. Определены распространенность и влияние на прогноз мутаций и полиморфизмов генов, кодирующих факторы свертывания крови (фактор V Лейден G1691A, протромбин G20210A, ß-фибриноген 455 G>A), рецептор тромбоцитов GPIIIa (C1565T) и ферменты, участвующие в обмене гомоцистеина (метилентетрагидрофолатредуктазу (MTHFR) C667 T и A1298C, метионинсинтазу (MTR) A2756G, метионинсинтазу-редуктазу (MTRR) A66G и транскобаламин (TCN) C776G). Результаты. Суммарная частота сосудистых событий составила 31,0%. Из всех изученных генетических показателей значимыми в отношении риска развития сосудистых событий оказались полиморфизмы MTHFR и TCN. Носительство хотя бы одной полиморфной аллели MTHFR 677 Т повышало риск развития ССО в 1,64 раза (95% доверительный интервал (ДИ) 1,2-2,3, р=0,003). Гомозиготное носительство «диких» генотипов MTHFR 1298 AА и TCN 776 СС повышало риск развития ССО, соответственно, в 1,63 раза (95% ДИ 1,2-2,3, р=0,006) и в 1,37 раза (95% ДИ 1,001-1,89, р=0,04). Влияние на прогноз генетических вариантов MTHFR C667 T/СТ и 1298 AА проявлялось при условии сопутствующего снижения уровня фолиевой кислоты плазмы крови, наблюдавшегося у 56,1% обследованных больных. Заключение. Выявление носительства генотипов MTHFR C667 T и 1298 AА, и TCN 776 СС, а также сопутствующее определение уровня фолиевой кислоты могут быть рекомендованы больным ИБС с целью уточнения риска развития неблагоприятных сердечно-сосудистых событий.

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