aterosklerozАтеросклерозAteroscleroz2078-256X2949-3633НИИТПМ-филиал ИЦиГ СО РАН10.15372/ATER20180302ateroskleroz-76Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПАНЕЛЬ ГЕНЕТИЧЕСКИХ МАРКЕРОВ ДЛЯ АНАЛИЗА РИСКА ОТДАЛЕННОГО НЕБЛАГОПРИЯТНОГО ПРОГНОЗА СЕРДЕЧНО-СОСУДИСТЫХ ЗАБОЛЕВАНИЙA PANEL OF GENETIC MARKERS FOR ANALYZING THE RISK OF LONG-TERM ADVERSE PROGNOSIS OF CARDIOVASCULAR DISEASESШахтшнейдерЕ. В.ShakhtshneiderE. V.noemail@neicon.ruОрловП. С.OrlovP. S.noemail@neicon.ruЩербаковаЛ. В.ShcherbakovaL. V.noemail@neicon.ruИванощукД. Е.IvanoshchukD. E.noemail@neicon.ruМалютинаС. К.MalyutinaS. K.noemail@neicon.ruМаксимовВ. Н.MaksimovV. N.noemail@neicon.ruГафаровВ. В.GafarovV. V.noemail@neicon.ruВоеводаМ. И.VoevodaM. I.noemail@neicon.ruНИИТПМ - филиал ИЦиГ СО РАНInstitute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RASНИИТПМ - филиал ИЦиГ СО РАН; ФИЦ Институт цитологии и генетики СО РАНInstitute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS; Federal Research Center Institute of Cytology and Genetics of SB RAS2018270920191431219Copyright © Шахтшнейдер Е.В., Орлов П.С., Щербакова Л.В., Иванощук Д.Е., Малютина С.К., Максимов В.Н., Гафаров В.В., Воевода М.И., 20192019Шахтшнейдер Е.В., Орлов П.С., Щербакова Л.В., Иванощук Д.Е., Малютина С.К., Максимов В.Н., Гафаров В.В., Воевода М.И.Shakhtshneider E.V., Orlov P.S., Shcherbakova L.V., Ivanoshchuk D.E., Malyutina S.K., Maksimov V.N., Gafarov V.V., Voevoda M.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ateroskleroz.elpub.ru/jour/article/view/76

Цель исследования: сформировать панель генетических маркеров для анализа риска развития отдаленного неблагоприятного прогноза сердечно-сосудистых заболеваний в российской популяции. Материал и методы. Выборка из 900 человек сформирована в рамках международного исследовательского проекта HAPIEE (возраст 45-69 лет, средний возраст 53,9±6,9, мужчины/женщины - 50/50). Молекулярно-генетический анализ выполнен методом ПЦР-ПДРФ для rs5128 гена APOC3 , rs429358 и rs7412 гена APOE , rs708272 гена CETP , rs320 гена LPL , rs5888 гена SCARB1 , rs2228314 гена SREBF2 . Результаты. Выполнен анализ 10 однонуклеотидных полиморфизмов для включения в рискометр неблагоприятного прогноза сердечно-сосудистых заболеваний в российской популяции. Генотип e4/e4 (rs429358 и rs7412) гена APOE ассоциирован с развитием неблагоприятных сердечно-сосудистых исходов в течение семи лет наблюдения. Для rs708272 гена CETP показана ассоциация с развитием случаев фатального инфаркта миокарда в течение семи лет наблюдения для генотипов, содержащих аллель С. Для rs5128 гена APOC3 , rs320 гена LPL , rs5888 гена SCARB1 , rs2228314 гена SREBF2 статистически значимой ассоциации с риском неблагоприятного прогноза сердечно-сосудистых заболеваний в пилотном исследовании получено не было. Заключение. Для генов APOE и CETP получены пилотные данные о наличии статистически значимой ассоциации с риском развития отдаленного неблагоприятного прогноза сердечно-сосудистых заболеваний в российской популяции.

Aim: to form a panel of genetic markers for analyzing the risk of long-term adverse prognosis of cardiovascular diseases in Russia population. Material and methods. A sample of nine hundred individuals was formed within the framework of the HAPIEE project (age 45-69 years, middle age 53.9 ± 6.9, male/female - 50/50). Molecular genetic analysis was performed using PCR followed by restriction fragment length polymorphism analysis for the APOC3 gene rs5128 polymorphism, APOE gene rs429358 and rs7412, CETP gene rs708272, LPL gene rs320, SCARB1 gene rs5888, and SREBF2 gene rs2228314 . Results. 10 single nucleotide polymorphisms were analyzed for the inclusion in the risk model of adverse prognosis of cardiovascular diseases in Russia population. The APOE gene e4/e4 genotype (rs429358 and rs7412) was associated with the development of adverse cardiovascular outcomes for 7 years of observation. For the CETP gene rs708272, the association with the development of cases of fatal myocardial infarction for 7 years of observation was demonstrated for the genotypes carrying C allele. No statistically significant association with the risk of adverse prognosis of cardiovascular diseases was obtained for the APOC3 gene rs5128, LPL gene rs320, SCARB1 gene rs5888, and SREBF2 gene rs2228314 in this pilot study. Conclusions. Pilot data on the presence of statistically significant association with the risk of long-term adverse prognosis of cardiovascular diseases in Russia population were obtained for the APOE and CETP genes.

генетический рискометрнеблагоприятные исходыинфаркт миокардасердечно-сосудистые заболеванияAPOECETPmodel of genetic riskunfavorable outcomesmyocardial infarctionAPOECETPcardiovascular diseasesReferencesОганов Р.Г., Масленникова Г.Я. Демографические тенденции в Российской Федерации: вклад болезней системы кровообращения // Кардиоваскулярная терапия и профилактика. 2012. Т. 11, № 1. С. 5-10.Оганов Р.Г., Масленникова Г.Я. Демографические тенденции в Российской Федерации: вклад болезней системы кровообращения // Кардиоваскулярная терапия и профилактика. 2012. Т. 11, № 1. С. 5-10.Amit V. Khera, Connor A. Emdin еt al. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease // N. Engl. J. Med. 2016. DOI: 10.1056/NEJMoa1605086.Amit V. Khera, Connor A. Emdin еt al. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease // N. Engl. J. Med. 2016. DOI: 10.1056/NEJMoa1605086.Ware J.H. The limitations of risk factors as prognostic tools // N. Engl. J. Med. 2006. Vol. 355. P. 2615-2617.Ware J.H. The limitations of risk factors as prognostic tools // N. Engl. J. Med. 2006. Vol. 355. P. 2615-2617.Stenlund H., Lцnnberg G., Jenkins P. et al. Fewer deaths from cardiovascular disease than expected from the Systematic Coronary Risk Evaluation chart in a Swedish population // Eur. J. Cardiovasc. Prev. Rehabil. 2009. Apr. 7.Stenlund H., Lцnnberg G., Jenkins P. et al. Fewer deaths from cardiovascular disease than expected from the Systematic Coronary Risk Evaluation chart in a Swedish population // Eur. J. Cardiovasc. Prev. Rehabil. 2009. Apr. 7.Lloyd-Jones D.M., Wilson P.W., Larson M.G. et al. Framingham risk score and prediction of lifetime risk for coronary heart disease // Am. J. Cardiol. 2004. Vol. 94. P. 20-24.Lloyd-Jones D.M., Wilson P.W., Larson M.G. et al. Framingham risk score and prediction of lifetime risk for coronary heart disease // Am. J. Cardiol. 2004. Vol. 94. P. 20-24.Ripatti S., Tikkanen E., Orho-Melander M. et al. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses // Lancet. 2010. Vol. 376. P. 1393-1400.Ripatti S., Tikkanen E., Orho-Melander M. et al. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses // Lancet. 2010. Vol. 376. P. 1393-1400.Thanassoulis G., Peloso G.M., Pencina M.J. et al. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study // Circ. Cardiovasc. Genet. 2012. Vol. 5. P. 113-121.Thanassoulis G., Peloso G.M., Pencina M.J. et al. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study // Circ. Cardiovasc. Genet. 2012. Vol. 5. P. 113-121.Brautbar A., Pompeii L.A., Dehghan A. et al. A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies // Atherosclerosis. 2012. Vol. 223. P. 421-426.Brautbar A., Pompeii L.A., Dehghan A. et al. A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies // Atherosclerosis. 2012. Vol. 223. P. 421-426.Mega J.L., Stitziel N.O., Smith J.G. et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials // Lancet. 2015. Vol. 385. P. 2264-2271.Mega J.L., Stitziel N.O., Smith J.G. et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials // Lancet. 2015. Vol. 385. P. 2264-2271.Tada H., Melander O., Louie J.Z. et al. Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history // Eur. Heart. J. 2016. Vol. 37. P. 561-567.Tada H., Melander O., Louie J.Z. et al. Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history // Eur. Heart. J. 2016. Vol. 37. P. 561-567.Peasey A., Bobak M., Kubinova R. et al. Determinants of cardiovascular disease and other non-communicable diseases in Central and Eastern Europe: Rationale and design of the HAPIEE study // BMC Public. Health. 2006. Vol. 6. P. 255.Peasey A., Bobak M., Kubinova R. et al. Determinants of cardiovascular disease and other non-communicable diseases in Central and Eastern Europe: Rationale and design of the HAPIEE study // BMC Public. Health. 2006. Vol. 6. P. 255.Sambrook J., Russell D.W. Purification of nucleic acids by extraction with phenol:chloroform // CSH Protoc. 2006. N 1.Sambrook J., Russell D.W. Purification of nucleic acids by extraction with phenol:chloroform // CSH Protoc. 2006. N 1.Mercer T.R., Dinger M.E., Mattick J.S. Long non-coding RNAs: insights into functions // Nat. Rev. Genet. 2009. Vol. 10, N 3. P. 155-159.Mercer T.R., Dinger M.E., Mattick J.S. Long non-coding RNAs: insights into functions // Nat. Rev. Genet. 2009. Vol. 10, N 3. P. 155-159.Chen G., Fu X., Wang G. et al. Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility // Int. J. Mol. Sci. 2015. Vol. 16, N 5. P. 11678-11688.Chen G., Fu X., Wang G. et al. Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility // Int. J. Mol. Sci. 2015. Vol. 16, N 5. P. 11678-11688.Орлов П.С., Ложкина Н.Г., Максимов В.Н. и др. Связь ряда однонуклеотидных полиморфизмов с инфарктом миокарда в разных возрастных группах европеоидов Новосибирска // Атеросклероз. 2017. Т. 13, № 2. С. 5-11.Орлов П.С., Ложкина Н.Г., Максимов В.Н. и др. Связь ряда однонуклеотидных полиморфизмов с инфарктом миокарда в разных возрастных группах европеоидов Новосибирска // Атеросклероз. 2017. Т. 13, № 2. С. 5-11.Goncharova I.A., Makeeva O.A., Golubenko M.V. et al. Genes for Fibrogenesis in the Determination of Susceptibility to Myocardial Infarction // Mol. Biol. (Mosk). 2016. Vol. 50. N 1. P. 94-105.Goncharova I.A., Makeeva O.A., Golubenko M.V. et al. Genes for Fibrogenesis in the Determination of Susceptibility to Myocardial Infarction // Mol. Biol. (Mosk). 2016. Vol. 50. N 1. P. 94-105.Шестерня П.А., Шульман В.А., Никулина С.Ю и др. Предикторная роль полиморфизмов хромосомы 9sр21.3 и их взаимосвязь с отягощенной наследственностью в развитии инфаркта миокарда // Рос. кардиол. журн. 2012. № 6 (98). С. 14-18.Шестерня П.А., Шульман В.А., Никулина С.Ю и др. Предикторная роль полиморфизмов хромосомы 9sр21.3 и их взаимосвязь с отягощенной наследственностью в развитии инфаркта миокарда // Рос. кардиол. журн. 2012. № 6 (98). С. 14-18.Ложкина Н.Г., Максимов В.Н., Куликов И.В. и др. Ассоциация генетических маркеров со сниженной сократительной функцией сердца у больных с острым коронарным синдромом // Медицина и образование в Сибири. 2013. № 3. С. 38.Ложкина Н.Г., Максимов В.Н., Куликов И.В. и др. Ассоциация генетических маркеров со сниженной сократительной функцией сердца у больных с острым коронарным синдромом // Медицина и образование в Сибири. 2013. № 3. С. 38.Singh P.P., Singh M., Mastana S.S. APOE distribution in world populations with new data from India and the UK // Аnn. Hum. Biol. 2006. Vol. 33. P. 279-308.Singh P.P., Singh M., Mastana S.S. APOE distribution in world populations with new data from India and the UK // Аnn. Hum. Biol. 2006. Vol. 33. P. 279-308.Hong Xu, Haiqing Li, Jun Liu. Meta-Analysis of Apolipoprotein E Gene Polymorphism and Susceptibility of Myocardial Infarction // PLoS One. 2014. Vol. 9, N 8. P. e104608.Hong Xu, Haiqing Li, Jun Liu. Meta-Analysis of Apolipoprotein E Gene Polymorphism and Susceptibility of Myocardial Infarction // PLoS One. 2014. Vol. 9, N 8. P. e104608.Воевода М.И., Шахтшнейдер Е.В., Куликов И.В. Ассоциация полиморфизма кодирующей части гена APOE с показателями липидного профиля в Новосибирске. Мониторирование сердечно-сосудистой заболеваемости, смертности и их факторов риска в разных регионах мира (проект ВОЗ MONICA). Новосибирск: Гео, 2016. С. 492-518.Воевода М.И., Шахтшнейдер Е.В., Куликов И.В. Ассоциация полиморфизма кодирующей части гена APOE с показателями липидного профиля в Новосибирске. Мониторирование сердечно-сосудистой заболеваемости, смертности и их факторов риска в разных регионах мира (проект ВОЗ MONICA). Новосибирск: Гео, 2016. С. 492-518.Shakhtshneider E.V., Ragino Y.I., Kulikov I.V., Ivanova M.V., Voevoda M.I., Chernjavski A.M. Apolipoprotein E gene polymorphism in men with coronary atherosclerosis in Siberia // Bull. Exp. Biol. Med. 2011. Vol. 150, N 3. P. 355-358.Shakhtshneider E.V., Ragino Y.I., Kulikov I.V., Ivanova M.V., Voevoda M.I., Chernjavski A.M. Apolipoprotein E gene polymorphism in men with coronary atherosclerosis in Siberia // Bull. Exp. Biol. Med. 2011. Vol. 150, N 3. P. 355-358.Kathiresan S. Common variants at 30 loci contribute to polygenic dyslipidemia // Nat. Genet. 2009. Vol. 8, N 14. P. 56-65.Kathiresan S. Common variants at 30 loci contribute to polygenic dyslipidemia // Nat. Genet. 2009. Vol. 8, N 14. P. 56-65.Шахтшнейдер Е.В., Куликов И.В., Максимов В.Н. и др. Полиморфизм гена CETP в европеоидной популяции Западной Сибири и группах, контрастных по уровню общего холестерина сыворотки // Бюл. эксперим. биологии и медицины. 2014. Т. 157, № 3. С. 343-347.Шахтшнейдер Е.В., Куликов И.В., Максимов В.Н. и др. Полиморфизм гена CETP в европеоидной популяции Западной Сибири и группах, контрастных по уровню общего холестерина сыворотки // Бюл. эксперим. биологии и медицины. 2014. Т. 157, № 3. С. 343-347.Ridker P.M., Pare G., Parker A.N. et al. Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: genomewide analysis among 18 245 initially healthy women from the women’s genome health study // Circ. Cardiovasc. Genet. 2009. Vol. 2, N 1. P. 26-33. DOI: 10.1161/circgenetics. 108.817304.Ridker P.M., Pare G., Parker A.N. et al. Polymorphism in the CETP gene region, HDL cholesterol, and risk of future myocardial infarction: genomewide analysis among 18 245 initially healthy women from the women’s genome health study // Circ. Cardiovasc. Genet. 2009. Vol. 2, N 1. P. 26-33. DOI: 10.1161/circgenetics. 108.817304.Qi Wang, Shao-Bo Zhou, Li-Jie Wang et. al. Seven Functional Polymorphisms in the CETP Gene and Myocardial Infarction Risk: A Meta-Analysis and Meta-Regression // PLoS One. 2014. Vol. 9, N 2. P. e88118.Qi Wang, Shao-Bo Zhou, Li-Jie Wang et. al. Seven Functional Polymorphisms in the CETP Gene and Myocardial Infarction Risk: A Meta-Analysis and Meta-Regression // PLoS One. 2014. Vol. 9, N 2. P. e88118.Johnson K., Farley D., Hu S.I. et al. One of two chondrocyte-expressed isoforms of cartilage intermediate-layer protein functions as an insulin-like growth factor 1 antagonist // Arthritis Rheum. 2003. Vol. 48, N 5. P. 1302-1314.Johnson K., Farley D., Hu S.I. et al. One of two chondrocyte-expressed isoforms of cartilage intermediate-layer protein functions as an insulin-like growth factor 1 antagonist // Arthritis Rheum. 2003. Vol. 48, N 5. P. 1302-1314.Willer C.J., Sanna S., Jackson A.U. et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease // Nat. Genet. 2008. Vol. 40, N 2. P. 161-169.Willer C.J., Sanna S., Jackson A.U. et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease // Nat. Genet. 2008. Vol. 40, N 2. P. 161-169.Hubacek J.A., Adamkova V., Lanska V. et al. Polygenic hypercholesterolemia: examples of GWAS results and their replication in the Czech-Slavonic population // Physiol. Res. 2017. Vol. 66, N 5 (Suppl. 1). P. S101-S111.Hubacek J.A., Adamkova V., Lanska V. et al. Polygenic hypercholesterolemia: examples of GWAS results and their replication in the Czech-Slavonic population // Physiol. Res. 2017. Vol. 66, N 5 (Suppl. 1). P. S101-S111.Tai E.S., Sim X.L., Ong T.H. et al. Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population // J. Lipid Res. 2009. Vol. 50, N 3. P. 514-520.Tai E.S., Sim X.L., Ong T.H. et al. Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population // J. Lipid Res. 2009. Vol. 50, N 3. P. 514-520.Ting-Ting Yan, Rui-Xing Yin, Qing Li. Sex-specific association of rs16996148 SNP in the NCAN/CILP2/PBX4 and serum lipid levels in the Mulao and Han populations // Lipids Health Dis. 2011. Vol. 10. P. 248.Ting-Ting Yan, Rui-Xing Yin, Qing Li. Sex-specific association of rs16996148 SNP in the NCAN/CILP2/PBX4 and serum lipid levels in the Mulao and Han populations // Lipids Health Dis. 2011. Vol. 10. P. 248.Lamina C., Kronenberg F. The mysterious lipoprotein(a) is still good for a surprise // Lancet Diabetes Endocrinol. 2013. Vol. 1. P. 170-172.Lamina C., Kronenberg F. The mysterious lipoprotein(a) is still good for a surprise // Lancet Diabetes Endocrinol. 2013. Vol. 1. P. 170-172.Luke M.M., Kane J.P., Liu D.M. et al. A polymorphism in the protease-like domain of apolipoprotein(a) is with severe coronary artery disease // Arterioscler. Thromb. Vasc. Biol. 2007. Vol. 27. P. 2030-2036.Luke M.M., Kane J.P., Liu D.M. et al. A polymorphism in the protease-like domain of apolipoprotein(a) is with severe coronary artery disease // Arterioscler. Thromb. Vasc. Biol. 2007. Vol. 27. P. 2030-2036.Chasman D.I., Shiffman D., Zee R.Y. et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy // Atherosclerosis. 2009. Vol. 203. P. 371-376.Chasman D.I., Shiffman D., Zee R.Y. et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy // Atherosclerosis. 2009. Vol. 203. P. 371-376.Clarke R., Peden J.F., Hopewell J.C. et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease // N. Engl. J. Med. 2009. Vol. 361, N 26. P. 2518-2528.Clarke R., Peden J.F., Hopewell J.C. et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease // N. Engl. J. Med. 2009. Vol. 361, N 26. P. 2518-2528.Li S., Wu N.Q., Zhu C.G. et al. Significance of lipoprotein(a) levels in familial hypercholesterolemia and coronary artery disease // Atherosclerosis. 2017. Vol. 260. P. 67-74. DOI: 10.1016/j.atherosclerosis. 2017.03.021.Li S., Wu N.Q., Zhu C.G. et al. Significance of lipoprotein(a) levels in familial hypercholesterolemia and coronary artery disease // Atherosclerosis. 2017. Vol. 260. P. 67-74. DOI: 10.1016/j.atherosclerosis. 2017.03.021.Rook M.B., Evers M.M., Vos M.A. et al. Biology of cardiac sodium channel Nav1.5 expression // Cardiovasc. Res. 2012. Vol. 93. P. 12-23.Rook M.B., Evers M.M., Vos M.A. et al. Biology of cardiac sodium channel Nav1.5 expression // Cardiovasc. Res. 2012. Vol. 93. P. 12-23.Schroeter A., Walzik S., Blechschmidt S. et al. Structure and function of splice variants of the cardiac voltage-gated sodium channel Na(v)1.5 // J. Mol. Cell Cardiol. 2010. Vol. 49. P. 16-24.Schroeter A., Walzik S., Blechschmidt S. et al. Structure and function of splice variants of the cardiac voltage-gated sodium channel Na(v)1.5 // J. Mol. Cell Cardiol. 2010. Vol. 49. P. 16-24.Tfelt-Hansen J., Winkel B.G., Grunnet M. et. аl. Inherited cardiac diseases caused by mutations in the Nav1.5 sodium channel // J. Cardiovasc. Electrophysiol. 2010. Vol. 21. P. 107-115.Tfelt-Hansen J., Winkel B.G., Grunnet M. et. аl. Inherited cardiac diseases caused by mutations in the Nav1.5 sodium channel // J. Cardiovasc. Electrophysiol. 2010. Vol. 21. P. 107-115.Matsumura H., Nakano Y., Ochi H. et al. H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters // J. Biomed. Sci. 2017. Vol. 24, N 1. P. 91.Matsumura H., Nakano Y., Ochi H. et al. H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters // J. Biomed. Sci. 2017. Vol. 24, N 1. P. 91.Qureshi S.F., Ali A., John P. et al. Mutational analysis of SCN5A gene in long QT syndrome // Meta Gene. 2015. Vol. 6. P. 26-35.Qureshi S.F., Ali A., John P. et al. Mutational analysis of SCN5A gene in long QT syndrome // Meta Gene. 2015. Vol. 6. P. 26-35.Nikulina S.Y., Chernova A.A., Shulman V.A. et al. An investigation of the association of the H558R polymorphism of the SCN5A gene with idiopathic cardiac conduction disorders // Genet. Test Mol. Biomarkers. 2015. Vol. 19, N 6. P. 288-294.Nikulina S.Y., Chernova A.A., Shulman V.A. et al. An investigation of the association of the H558R polymorphism of the SCN5A gene with idiopathic cardiac conduction disorders // Genet. Test Mol. Biomarkers. 2015. Vol. 19, N 6. P. 288-294.Макеева О.А., Зыков М.В., Голубенко М.В. и др. Роль генетических факторов в прогнозировании осложнений на протяжении года после инфаркта миокарда // Кардиология. 2013. Т. 53, № 10. С. 16-23.Макеева О.А., Зыков М.В., Голубенко М.В. и др. Роль генетических факторов в прогнозировании осложнений на протяжении года после инфаркта миокарда // Кардиология. 2013. Т. 53, № 10. С. 16-23.Mannucci P.M., Asselta R., Duga S. et al. The association of factor V Leiden with myocardial infarction is replicated in 1880 patients with premature disease // J. Thromb. Haemost. 2010. Vol. 8, N 1. P. 2116-2121.Mannucci P.M., Asselta R., Duga S. et al. The association of factor V Leiden with myocardial infarction is replicated in 1880 patients with premature disease // J. Thromb. Haemost. 2010. Vol. 8, N 1. P. 2116-2121.Li C., Ren H., Chen H. et al. Prothrombin G20210A (rs1799963) polymorphism increases myocardial infarction risk in an age-related manner: A systematic review and meta-analysis // Sci. Rep. 2017. Vol. 7, N 1. P. 13550.Li C., Ren H., Chen H. et al. Prothrombin G20210A (rs1799963) polymorphism increases myocardial infarction risk in an age-related manner: A systematic review and meta-analysis // Sci. Rep. 2017. Vol. 7, N 1. P. 13550.Tomaiuolo Rossella, Bellia Chiara, Caruso Antonietta et al. Prothrombotic gene variants as risk factors of acute myocardial infarction in young women // J. Transl. Med. 2012. Vol. 10. P. 235.Tomaiuolo Rossella, Bellia Chiara, Caruso Antonietta et al. Prothrombotic gene variants as risk factors of acute myocardial infarction in young women // J. Transl. Med. 2012. Vol. 10. P. 235.Pollin T.I., Damcott C.M., Shen H. et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection // Science. 2008. Vol. 322 (5908). P. 1702-1705. DOI: 10.1126/science.1161524.Pollin T.I., Damcott C.M., Shen H. et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection // Science. 2008. Vol. 322 (5908). P. 1702-1705. DOI: 10.1126/science.1161524.Adams J.N., Raffield L.M., Freedman B.I. et. al. Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study // Cardiovasc. Diabetol. 2014. Vol. 13. P. 77. DOI: 10.1186/1475-2840-13-77.Adams J.N., Raffield L.M., Freedman B.I. et. al. Analysis of common and coding variants with cardiovascular disease in the Diabetes Heart Study // Cardiovasc. Diabetol. 2014. Vol. 13. P. 77. DOI: 10.1186/1475-2840-13-77.Song Y., Zhu L., Richa M. et. al. Associations of the APOC3 rs5128 polymorphism with plasma APOC3 and lipid levels: a meta-analysis // Lipids Health Dis. 2015. Vol. 14. P. 32. DOI: 10.1186/s12944-015-0027-0.Song Y., Zhu L., Richa M. et. al. Associations of the APOC3 rs5128 polymorphism with plasma APOC3 and lipid levels: a meta-analysis // Lipids Health Dis. 2015. Vol. 14. P. 32. DOI: 10.1186/s12944-015-0027-0.Bommer G.T., MacDougald O.A. Regulation of lipid homeostasis by the bifunctional SREBF2-miR33a locus // Cell Metab. 2011. Vol. 13, N 3. P. 241-247. DOI: 10.1016/j.cmet.2011.02.004.Bommer G.T., MacDougald O.A. Regulation of lipid homeostasis by the bifunctional SREBF2-miR33a locus // Cell Metab. 2011. Vol. 13, N 3. P. 241-247. DOI: 10.1016/j.cmet.2011.02.004.Najafi-Shoushtari S.H., Kristo F., Li Y. et. al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis // Science. 2010. Vol. 328 (5985). P. 1566-1569. DOI: 10.1126/science. 1189123.Najafi-Shoushtari S.H., Kristo F., Li Y. et. al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis // Science. 2010. Vol. 328 (5985). P. 1566-1569. DOI: 10.1126/science. 1189123.Pйrez-Belmonte L.M., Moreno-Santos I., Cabrera-Bueno F. et al. Expression of Sterol Regulatory Element-Binding Proteins in epicardial adipose tissue in patients with coronary artery disease and diabetes mellitus: preliminary study // Int. J. Med. Sci. 2017. Vol. 14, N 3. P. 268-274. DOI: 10.7150/ijms.17821. eCollection 2017.Pйrez-Belmonte L.M., Moreno-Santos I., Cabrera-Bueno F. et al. Expression of Sterol Regulatory Element-Binding Proteins in epicardial adipose tissue in patients with coronary artery disease and diabetes mellitus: preliminary study // Int. J. Med. Sci. 2017. Vol. 14, N 3. P. 268-274. DOI: 10.7150/ijms.17821. eCollection 2017.

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