cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLCcardiovascular-2060Research ArticleИШЕМИЧЕСКАЯ БОЛЕЗНЬ СЕРДЦАCORONARY HEART DISEASEПрогностическая значимость носительства аллельных вариантов генов, контролирующих систему гемостаза, и их сочетания с традиционными факторами риска в раннем развитии ишемической болезни сердцаPrognostic role of hemostasis-regulating genetic factors and their interaction with conventional risk factors at the early stages of coronary heart disease developmentАндреенкоЕ. Ю.AndreenkoE. Yu.

научный сотрудник отдела клинической кардиологии и молекулярной генетики

Москва

Moscow

elena.andreenko@gmail.comСамоходскаяЛ. М.SamokhodskayaL. M.

ст. научный сотрудник лаборатории генных и клеточных технологий факультета фундаментальной медицины

Москва

Moscow

БалацкийА. В.BalatskyiA. V.

аспирант кафедры медицинской и биологической химии факультета фундаментальной медицины

Москва

Moscow

МакаревичП. И.MakarevichP. I.

аспирант кафедры медицинской и биологической химии факультета фундаментальной медицины

Москва

Moscow

БойцовС. А.BoytsovS. A.

директор

Москва

Moscow

Государственный научно-исследовательский центр профилактической медициныState Research Centre for Preventive MedicineМосковский государственный университет имени М. В. ЛомоносоваM. V. Lomonosov Moscow State University2011010119701083239Copyright © Андреенко Е.Ю., Самоходская Л.М., Балацкий А.В., Макаревич П.И., Бойцов С.А., 19701970Андреенко Е.Ю., Самоходская Л.М., Балацкий А.В., Макаревич П.И., Бойцов С.А.Andreenko E.Y., Samokhodskaya L.M., Balatskyi A.V., Makarevich P.I., Boytsov S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/2060

Цель. Определить прогностическую значимость носительства аллельных вариантов генов факторов свертывания крови и их сочетания с негенетическими факторами риска (ФР): курение, артериальная гипертония (АГ), гиперхолестеринемия (ГХС), ожирение (Ож), в раннем развитии ишемической болезни сердца (ИБС), в т. ч. инфаркта миокарда (ИМ) у больных ИБС. Материал и методы. Обследованы 977 мужчин в возрасте 20–55 лет: 375 больных ИБС, в т. ч.: 186 – без ИМ, 189 – с ИМ в анамнезе и 602 человека без сердечно-сосудистых заболеваний (ССЗ). Проведен анализ полиморфизма генов тромбоцитарных рецепторов гликопротеина Ia (C807T) и гликопротеина IIIa (PLA1/PLA2); полиморфизма генов, кодирующих белки свертывающей и противосвертывающей систем крови: полиморфизм R353Q VII фактора, V34L XIII фактора свертывания крови и инсерционно-делеционный полиморфизм 4G/5G ингибитора активатора плазминогена 1 типа, а также их сочетания с традиционными ФР: курение, АГ, ГХС, Ож. Для определения аллельных вариантов исследуемых генов использовали метод полимеразной цепной реакции (ПЦР) с анализом длины рестриктных фрагментов, аллельспецифичной ПЦР и метод ПЦР в режиме «реального времени». Результаты. С повышенным риском формирования ИБС ассоциировался генотип ТТ гена GPIa (p=0,0001) (OR=10,2). С уменьшением риска развития ИБС ассоциировались генотип LL FXIII (p=0,03) (OR=0,48) и генотип QQ FVII свертывания крови (p=0,01) (OR=0,12), а сочетание L-аллеля гена FXIII с Q аллелем FVII ассоциировалось с уменьшением риска развития ИМ как осложнения ИБС (p=0,03) (OR=0,33). Анализ сочетаний генотипов с традиционными ФР показал, что PLA2/PLA2 генотип GPIIIa у больных с ГХС повышает риск развития ИМ у больных ИБС (p=0,01) (OR=6,0). Заключение. В алгоритм генетической диагностики предрасположенности к раннему развитию ИБС могут быть включены: полиморфизм C807T гена гликопротеина Ia, PLA1/PLA2 гена гликопротеина IIIa, V34L гена А-субъединицы фактора XIII свертывания крови и R304Q гена фактора VII свертывания крови. В исследовании не нашло подтверждение негативное влияние полиморфизма 4G/5G гена PAI-1 на развитие ИБС и ИМ.

Aim. To investigate the prognostic role of selected single nucleotide polymorphisms in hemostasis-regulating genes and to clarify their interaction with conventional risk factors, RF (smoking, arterial hypertension (AH), hypercholesterolemia (HCH), obesity (O)) at the early stages of coronary heart disease (CHD) development, with or without subsequent myocardial infarction (MI). Material and methods. The study included 977 men aged 20–55 years: 375 CHD patients (189 and 186 with or without previous MI, respectively) and 602 individuals without cardiovascular disease (CVD). Exclusion criteria were diabetes mellitus and impaired glucose tolerance. The authors analysed the polymorphisms of thrombocyte receptor genes GPIa (C807T) and GPIIIa (PLA1/PLA2); coagulation and fibrinolytic protein genes for factor VII (R353Q) and factor XIII (V34L); and the plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism. The association of these polymorphisms with conventional RF (smoking, AH, HCH, and O) was also investigated. To identify genetic variations, a restriction fragment length polymorphism assay, allele-specific assay, and fluorescence primer-probe assay were used. Results. Increased CHD risk was associated with the TT genotype of GPIa (p=0,0001; OR=10,2). The LL genotype of FXIII (p=0,03; OR=0,48) and QQ genotype of FVII (p=0,01; OR=0,12) were linked to reduced CHD risk. The combination of FXIII L allele and FVII Q allele was associated with a lower MI risk in CHD patients (p=0,03; OR=0,33). In participants with HCH, the PLA2/PLA2 genotype of GPIIIa was linked to increased MI risk for CHD patients (p=0,01; OR=6,0). Conclusion. The algorithm for predicting the genetic CHD risk may incorporate the assessment of the genetic polymorphism of GPIa (C807T), GPIIIa (PLA1/PLA2), factor XIII (V34L), and factor VII (R353Q). The study results did not confirm the negative effect of the PAI-1 gene 4G/5G polymorphism on CHD risk.

ишемическая болезнь сердцаинфаркт миокардаполиморфизм геновгемостазгликопротеин Iaгликопротеин IIIaингибитор активатора плазминогена 1 типафактор XIIIфактор VIICoronary heart diseasemyocardial infarctiongenetic polymorphismhemostasisglycoprotein Iaglycoprotein IIIaplasminogen activator inhibitor-1factor XIIIfactor VIIРабота выполнена при финансовой поддержке Межфакультетского проекта МГУ им. М. В. Ломоносова «Постгеномные медицинские исследования и технологии. Продление жизни и улучшение здоровья человека» Договор № 34 от «20» апреля 2009 г.ReferencesПанченко Е. П., Добровольский А. Б. Тромбозы в кардиологии. Механизмы развития и возможности терапии. М: Спорт и культура 1999; 464.Панченко Е. П., Добровольский А. Б. Тромбозы в кардиологии. Механизмы развития и возможности терапии. М: Спорт и культура 1999; 464.Humphries SE, Yiannakouris N, Talmud PJ. Cardiovascular disease risk prediction using genetic information (gene scores): is it really informative? Curr Opin Lipidol 2008; 19 (2): 128–32.Humphries SE, Yiannakouris N, Talmud PJ. Cardiovascular disease risk prediction using genetic information (gene scores): is it really informative? Curr Opin Lipidol 2008; 19 (2): 128–32.Schunkert H, Konig IR, Erdmann J. Molecular signatures of cardiovascular disease risk: potential for test development and clinical application. Mol Diagn Ther 2008; 12 (5): 281–7.Schunkert H, Konig IR, Erdmann J. Molecular signatures of cardiovascular disease risk: potential for test development and clinical application. Mol Diagn Ther 2008; 12 (5): 281–7.Humphries SE, Ridker PM, Talmud PJ. Genetic testing for cardiovascular disease susceptibility: a useful clinical management tool or possible misinformation? Arterioscler Thromb Vasc Biol 2004; 24 (4): 628–36.Humphries SE, Ridker PM, Talmud PJ. Genetic testing for cardiovascular disease susceptibility: a useful clinical management tool or possible misinformation? Arterioscler Thromb Vasc Biol 2004; 24 (4): 628–36.Damani SB, Topol EJ. Future use of genomics in coronary artery disease. JACC 2007; 50 (20): 1933–40.Damani SB, Topol EJ. Future use of genomics in coronary artery disease. JACC 2007; 50 (20): 1933–40.Avard D, Knoppers BM. Genomic medicine: considerations for health professionals and the public. Genome Med 2009; 1 (2): 25.Avard D, Knoppers BM. Genomic medicine: considerations for health professionals and the public. Genome Med 2009; 1 (2): 25.Vanhoutte PM. Endothelial dysfunction: the first step toward coronary arteriosclerosis. Circ J 2009; 73 (4): 595–601.Vanhoutte PM. Endothelial dysfunction: the first step toward coronary arteriosclerosis. Circ J 2009; 73 (4): 595–601.Ardissino D, Mannucci PM, Merlini PA, et al. Prothrombotic genetic risk factors in young survivors of myocardial infarction. Blood 1999; 94 (1): 46–51.Ardissino D, Mannucci PM, Merlini PA, et al. Prothrombotic genetic risk factors in young survivors of myocardial infarction. Blood 1999; 94 (1): 46–51.Humphries SE, Luong LA, Ogg MS, et al. The interleukin-6 –174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J 2001; 22 (24): 2243–52.Humphries SE, Luong LA, Ogg MS, et al. The interleukin-6 –174 G/C promoter polymorphism is associated with risk of coronary heart disease and systolic blood pressure in healthy men. Eur Heart J 2001; 22 (24): 2243–52.Приказ Министерства здравоохранения Российской Федерации от 14 сентября 2001 г. № 364 “Об утверждении Порядка медицинского обследования донора крови и ее компонентов” 2001.Приказ Министерства здравоохранения Российской Федерации от 14 сентября 2001 г. № 364 “Об утверждении Порядка медицинского обследования донора крови и ее компонентов” 2001.Calverley DC, Baldermann LV, Moran K, et al. Platelet FcgammaRIIA expression is associated with the alpha2 integrin C807T gene polymorphism in type 2 diabetes. Platelets 2006; 17 (2): 78–83.Calverley DC, Baldermann LV, Moran K, et al. Platelet FcgammaRIIA expression is associated with the alpha2 integrin C807T gene polymorphism in type 2 diabetes. Platelets 2006; 17 (2): 78–83.Dinauer DM, Friedman KD, Hessner MJ. Allelic distribution of the glycoprotein Ia (alpha2-integrin) C807T/G873A dimorphisms among caucasian venous thrombosis patients and six racial groups. Br J Haematol 1999; 107 (3): 563–5.Dinauer DM, Friedman KD, Hessner MJ. Allelic distribution of the glycoprotein Ia (alpha2-integrin) C807T/G873A dimorphisms among caucasian venous thrombosis patients and six racial groups. Br J Haematol 1999; 107 (3): 563–5.Ye Z, Liu EH, Higgins JP, et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006; 367 (9511): 651–8.Ye Z, Liu EH, Higgins JP, et al. Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls. Lancet 2006; 367 (9511): 651–8.Morita H, Kurihara H, Imai Y, et al. Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and myocardial infarction in Japanese. An approach entailing melting curve analysis with specific fluorescent hybridization probes. Thromb Haemost 2001; 85 (2): 226–30.Morita H, Kurihara H, Imai Y, et al. Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and myocardial infarction in Japanese. An approach entailing melting curve analysis with specific fluorescent hybridization probes. Thromb Haemost 2001; 85 (2): 226–30.Lewandowski K, Swierczynska A, Kwasnikowski P, et al. The prevalence of C807T mutation of glycoprotein Ia gene among young male survivors of myocardial infarction: a relation with coronary angiography results. Kardiol Pol 2005; 63 (2): 107–13; discussion114.Lewandowski K, Swierczynska A, Kwasnikowski P, et al. The prevalence of C807T mutation of glycoprotein Ia gene among young male survivors of myocardial infarction: a relation with coronary angiography results. Kardiol Pol 2005; 63 (2): 107–13; discussion114.Tsantes AE, Nikolopoulos GK, Bagos PG, et al. Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and coronary artery disease: a meta-analysis. Int J Cardiol 2007; 118 (2): 189–96.Tsantes AE, Nikolopoulos GK, Bagos PG, et al. Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and coronary artery disease: a meta-analysis. Int J Cardiol 2007; 118 (2): 189–96.Giusti B, Gori AM, Marcucci R, et al. Role of glycoprotein Ia gene polymorphisms in determining platelet function in myocardial infarction patients undergoing percutaneous coronary intervention on dual antiplatelet treatment. Atherosclerosis 2008; 196 (1): 341–8.Giusti B, Gori AM, Marcucci R, et al. Role of glycoprotein Ia gene polymorphisms in determining platelet function in myocardial infarction patients undergoing percutaneous coronary intervention on dual antiplatelet treatment. Atherosclerosis 2008; 196 (1): 341–8.Antoniades C, Tousoulis D, Vasiliadou C, et al. Genetic polymorphisms of platelet glycoprotein Ia and the risk for premature myocardial infarction: effects on the release of sCD40L during the acute phase of premature myocardial infarction. JACC 2006; 47 (10): 1959–66.Antoniades C, Tousoulis D, Vasiliadou C, et al. Genetic polymorphisms of platelet glycoprotein Ia and the risk for premature myocardial infarction: effects on the release of sCD40L during the acute phase of premature myocardial infarction. JACC 2006; 47 (10): 1959–66.Newman PJ, Derbes RS, Aster RH. The human platelet alloantigens, PLA1 and PLA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J Clin Invest 1989; 83 (5): 1778–81.Newman PJ, Derbes RS, Aster RH. The human platelet alloantigens, PLA1 and PLA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J Clin Invest 1989; 83 (5): 1778–81.Honda S, Honda Y, Bauer B, et al. The impact of threedimensional structure on the expression of PlA alloantigens on human integrin beta 3. Blood 1995; 86 (1): 234–42.Honda S, Honda Y, Bauer B, et al. The impact of threedimensional structure on the expression of PlA alloantigens on human integrin beta 3. Blood 1995; 86 (1): 234–42.Zhu MM, Weedon J, Clark LT. Meta-analysis of the association of platelet glycoprotein IIIa PLA1/A2 polymorphism with myocardial infarction. Am J Cardiol 2000; 86 (9): 1000–5, A8.Zhu MM, Weedon J, Clark LT. Meta-analysis of the association of platelet glycoprotein IIIa PLA1/A2 polymorphism with myocardial infarction. Am J Cardiol 2000; 86 (9): 1000–5, A8.Aleksic N, Juneja H, Folsom AR, et al. Platelet Pl (A2) allele and incidence of coronary heart disease: results from the Atherosclerosis Risk In Communities (ARIC) Study. Circulation 2000; 102 (16): 1901–5.Aleksic N, Juneja H, Folsom AR, et al. Platelet Pl (A2) allele and incidence of coronary heart disease: results from the Atherosclerosis Risk In Communities (ARIC) Study. Circulation 2000; 102 (16): 1901–5.Lanni F, Santulli G, Izzo R, et al. The Pl (A1/A2) polymorphism of glycoprotein IIIa and cerebrovascular events in hypertension: increased risk of ischemic stroke in high-risk patients. J Hypertens 2007; 25 (3): 551–6.Lanni F, Santulli G, Izzo R, et al. The Pl (A1/A2) polymorphism of glycoprotein IIIa and cerebrovascular events in hypertension: increased risk of ischemic stroke in high-risk patients. J Hypertens 2007; 25 (3): 551–6.O’Halloran AM, Curtin R, O’Connor F, et al. The impact of genetic variation in the region of the GPIIIa gene, on Pl expression bias and GPIIb/IIIa receptor density in platelets. Br J Haematol 2006; 132 (4): 494–502.O’Halloran AM, Curtin R, O’Connor F, et al. The impact of genetic variation in the region of the GPIIIa gene, on Pl expression bias and GPIIb/IIIa receptor density in platelets. Br J Haematol 2006; 132 (4): 494–502.Feng D, Lindpaintner K, Larson MG, et al. Increased platelet aggregability associated with platelet GPIIIa PLA2 polymorphism: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 1999; 19 (4): 1142–7.Feng D, Lindpaintner K, Larson MG, et al. Increased platelet aggregability associated with platelet GPIIIa PLA2 polymorphism: the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 1999; 19 (4): 1142–7.Mikkelsson J, Perola M, Penttila A, et al. The GPIIIa (beta3 integrin) PlA polymorphism in the early development of coronary atherosclerosis. Atherosclerosis. 2001. 154 (3): 721–7.Mikkelsson J, Perola M, Penttila A, et al. The GPIIIa (beta3 integrin) PlA polymorphism in the early development of coronary atherosclerosis. Atherosclerosis. 2001. 154 (3): 721–7.Ross R. Atherosclerosis is an inflammatory disease. Am Heart J 1999; 138 (5 Pt 2): S419–20.Ross R. Atherosclerosis is an inflammatory disease. Am Heart J 1999; 138 (5 Pt 2): S419–20.Yamada Y, Izawa H, Ichihara S, et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med 2002; 347 (24): 1916–23.Yamada Y, Izawa H, Ichihara S, et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med 2002; 347 (24): 1916–23.Ye S, Green FR, Scarabin PY, et al. The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Etude CasTemoins de I’nfarctus du Mycocarde. Thromb Haemost 1995; 74 (3): 837–41.Ye S, Green FR, Scarabin PY, et al. The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Etude CasTemoins de I’nfarctus du Mycocarde. Thromb Haemost 1995; 74 (3): 837–41.Leander K, Wiman B, Hallqvist J, et al. PAI-1 level and the PAI-1 4G/5G polymorphism in relation to risk of nonfatal myocardial infarction: results from the Stockholm Heart Epidemiology Program (SHEEP). Thromb Haemost 2003; 89 (6): 1064–71.Leander K, Wiman B, Hallqvist J, et al. PAI-1 level and the PAI-1 4G/5G polymorphism in relation to risk of nonfatal myocardial infarction: results from the Stockholm Heart Epidemiology Program (SHEEP). Thromb Haemost 2003; 89 (6): 1064–71.Kathiresan S, Gabriel SB, Yang Q, et al. Comprehensive survey of common genetic variation at the plasminogen activator inhibitor-1 locus and relations to circulating plasminogen activator inhibitor-1 levels. Circulation 2005; 112 (12): 1728–35.Kathiresan S, Gabriel SB, Yang Q, et al. Comprehensive survey of common genetic variation at the plasminogen activator inhibitor-1 locus and relations to circulating plasminogen activator inhibitor-1 levels. Circulation 2005; 112 (12): 1728–35.Andersen MD, Kjalke M, Bang S, et al. Coagulation factor XIII variants with altered thrombin activation rates. Biol Chem 2009; 390 (12): 1279–83.Andersen MD, Kjalke M, Bang S, et al. Coagulation factor XIII variants with altered thrombin activation rates. Biol Chem 2009; 390 (12): 1279–83.Siegerink B, Algra A, Rosendaal FR. Genetic variants of coagulation factor XIII and the risk of myocardial infarction in young women. Br J Haematol 2009; 146 (4): 459–61.Siegerink B, Algra A, Rosendaal FR. Genetic variants of coagulation factor XIII and the risk of myocardial infarction in young women. Br J Haematol 2009; 146 (4): 459–61.Bereczky Z, Balogh E, Katona E, et al. Decreased factor XIII levels in factor XIII A subunit Leu34 homozygous patients with coronary artery disease. Thromb Res 2008; 121 (4): 469–76.Bereczky Z, Balogh E, Katona E, et al. Decreased factor XIII levels in factor XIII A subunit Leu34 homozygous patients with coronary artery disease. Thromb Res 2008; 121 (4): 469–76.Rallidis LS, Politou M, Komporozos C, et al. Factor XIII Val34Leu polymorphism and the risk of myocardial infarction under the age of 36 years. Thromb Haemost 2008; 99 (6): 1085–9.Rallidis LS, Politou M, Komporozos C, et al. Factor XIII Val34Leu polymorphism and the risk of myocardial infarction under the age of 36 years. Thromb Haemost 2008; 99 (6): 1085–9.Attie-Castro FA, Zago MA, Lavinha J, et al. Ethnic heterogeneity of the factor XIII Val34Leu polymorphism. Thromb Haemost 2000; 84 (4): 601–3.Attie-Castro FA, Zago MA, Lavinha J, et al. Ethnic heterogeneity of the factor XIII Val34Leu polymorphism. Thromb Haemost 2000; 84 (4): 601–3.Boekholdt SM, Sandhu MS, Wareham NJ, et al. Fibrinogen plasma levels modify the association between the factor XIII Val34Leu variant and risk of coronary artery disease: the EPIC-Norfolk prospective population study. J Thromb Haemost 2006; 4 (10): 2204–9.Boekholdt SM, Sandhu MS, Wareham NJ, et al. Fibrinogen plasma levels modify the association between the factor XIII Val34Leu variant and risk of coronary artery disease: the EPIC-Norfolk prospective population study. J Thromb Haemost 2006; 4 (10): 2204–9.Feng D, Tofler GH, Larson MG, et al. Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 2000; 20 (2): 593–600.Feng D, Tofler GH, Larson MG, et al. Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 2000; 20 (2): 593–600.Sanders TA, de Grassi T, Miller GJ, et al. Dietary oleic and palmitic acids and postprandial factor VII in middleaged men heterozygous and homozygous for factor VII R353Q polymorphism. Am J Clin Nutr 1999; 69 (2): 220–5.Sanders TA, de Grassi T, Miller GJ, et al. Dietary oleic and palmitic acids and postprandial factor VII in middleaged men heterozygous and homozygous for factor VII R353Q polymorphism. Am J Clin Nutr 1999; 69 (2): 220–5.Wu AH, Tsongalis GJ. Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases. Am J Cardiol 2001; 87 (12): 1361–6.Wu AH, Tsongalis GJ. Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases. Am J Cardiol 2001; 87 (12): 1361–6.Maitland-van der Zee AH, Peters BJ, Lynch AI, et al. The effect of nine common polymorphisms in coagulation factor genes (F2, F5, F7, F12 and F13) on the effectiveness of statins: the GenHAT study. Pharmacogenet Genomics 2009; 19 (5): 338–44.Maitland-van der Zee AH, Peters BJ, Lynch AI, et al. The effect of nine common polymorphisms in coagulation factor genes (F2, F5, F7, F12 and F13) on the effectiveness of statins: the GenHAT study. Pharmacogenet Genomics 2009; 19 (5): 338–44.Drenos F, Talmud PJ, Casas JP, et al. Integrated associations of genotypes with multiple blood biomarkers linked to coronary heart disease risk. Hum Mol Genet 2009; 18 (12): 2305–16.Drenos F, Talmud PJ, Casas JP, et al. Integrated associations of genotypes with multiple blood biomarkers linked to coronary heart disease risk. Hum Mol Genet 2009; 18 (12): 2305–16.Xu G, Jin GD, Fu GS, et al. Association of coagulation factor V, VII gene polymorphisms with coronary heart disease. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2003; 20 (1): 39–42.Xu G, Jin GD, Fu GS, et al. Association of coagulation factor V, VII gene polymorphisms with coronary heart disease. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2003; 20 (1): 39–42.Yang Q, Kathiresan S, Lin JP, et al. Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study. BMC Med Genet 2007; 8 Suppl 1: S12.Yang Q, Kathiresan S, Lin JP, et al. Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study. BMC Med Genet 2007; 8 Suppl 1: S12.Lindman AS, Pedersen JI, Arnesen H, et al. Coagulation factor VII, R353Q polymorphism, and serum choline-containing phospholipids in males at high risk for coronary heart disease. Thromb Res 2004; 113 (1): 57–65.Lindman AS, Pedersen JI, Arnesen H, et al. Coagulation factor VII, R353Q polymorphism, and serum choline-containing phospholipids in males at high risk for coronary heart disease. Thromb Res 2004; 113 (1): 57–65.

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