Роль генетических факторов в формировании индивидуальной предрасположенности к ишемическому инсульту

Обложка


Цитировать

Полный текст

Аннотация

Интенсивное развитие технологий анализа ДНК и масштабные исследования полногеномных ассоциаций привели к накоплению большого массива данных о связи генетических факторов с различными фенотипическими проявлениями, в т.ч. с моногенными и полигенными наследственными заболеваниями. Благодаря этому значительно расширились возможности клинической диагностики и предиктивной медицины в области социально значимых заболеваний. Так, в настоящее время активно развиваются исследования генетического компонента в формировании риска развития такого многофакторного и полиэтиологического заболевания, как инсульт. В крупномасштабных исследованиях выявлены как общие, так и специфические генетические маркеры, ассоциированные только с инсультом определенного типа и подтипа. В настоящем обзоре проведен анализ современного состояния проблемы использования генетических маркеров для диагностики предрасположенности к инсульту, сложных вопросов, связанных с множественностью факторов риска инсульта, а также возможных путей развития данного направления.

Об авторах

Виталий Иванович Корчагин

ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора

Email: vitaly_korchagin@rambler.ru
Россия, Москва

K. O. Миронов

ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора

Email: vitaly_korchagin@rambler.ru
Россия, Москва

O. П. Дрибноходова

ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора

Email: vitaly_korchagin@rambler.ru
Россия, Москва

Марина Юрьевна Максимова

ФГБНУ «Научный центр неврологии»

Email: vitaly_korchagin@rambler.ru
ORCID iD: 0000-0002-7682-6672
Россия, Москва, Волоколамское шоссе, 80

Сергей Николаевич Иллариошкин

ФГБНУ «Научный центр неврологии»

Email: vitaly_korchagin@rambler.ru
ORCID iD: 0000-0002-2704-6282

д.м.н., проф., член-корр. РАН, зам. директора по научной работе, рук. отдела исследований мозга

Россия, Москва

Маринэ Мовсесовна Танашян

ФГБНУ «Научный центр неврологии»

Email: vitaly_korchagin@rambler.ru
ORCID iD: 0000-0002-5883-8119

д.м.н., профессор, член-корреспондент РАН, зам. директора по научной работе, рук. 1-го неврологического отделения

Россия, Москва

A. И. Платонов

ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора

Email: vitaly_korchagin@rambler.ru
Россия, Москва

Г. A. Шипулин

ФБУН «Центральный НИИ эпидемиологии» Роспотребнадзора

Email: vitaly_korchagin@rambler.ru
Россия, Москва

Антон Алексеевич Раскуражев

ФГБНУ «Научный центр неврологии»

Email: vitaly_korchagin@rambler.ru
ORCID iD: 0000-0003-0522-767X

к.м.н., врач-невролог, с.н.с. 1-го неврологического отделения

Россия, Москва

Михаил Александрович Пирадов

ФГБНУ «Научный центр неврологии»

Автор, ответственный за переписку.
Email: vitaly_korchagin@rambler.ru
ORCID iD: 0000-0002-6338-0392

д.м.н., проф., академик РАН, директор

Россия, Москва

Список литературы

  1. Давиденкова Е.Ф., Колесова Н.Н., Либерман И.С. Медико-генетическое консультирование в системе профилактики ишемической болезни сердца и инсультов. Л.: Медицина, 1979.
  2. Козловская Н.Л. Тромбофилические состояния. Клиническая фармакология и терапия 2003; 12: 74–80.
  3. Платонов А.Е. Статистический анализ в медицине и биологии: задачи, терминология, логика, компьютерные методы. М.: Изд. РАМН, 2000.
  4. Суслина З.А., Иллариошкин С.Н., Пирадов М.А. Неврология и нейронауки – прогноз развития. Анн. клинич. и эксперим. неврол. 2007; 1: 5–9.
  5. Adams H.P., Bendixen B.H., Kappelle L.J. et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. Stroke 1993; 24 (1): 35–41.
  6. Alison E. Baird Genetics and Genomics of Stroke. Novel Approaches. J. Am. Coll. Cardiol. 2010; 56 (4): 245–253.
  7. Andre C. CADASIL: pathogenesis, clinical and radiological findings and treatment. Arq. Neuropsiquiatr. 2010; 68 (2): 287–299.
  8. Aznar J., Mira Y., Vaya A. et al. Factor V Leiden and prothrombin G20210A mutations in young adults with cryptogenic ischemic stroke. Thromb. Haemost. 2004; 91 (5): 1031–1034.
  9. Baker R.I., Eikelboom J., Lofthouse E. et al. Platelet glycoprotein Ib alpha Kozak polymorphism is associated with an increased risk of ischemic stroke. Blood 2001; 98 (1): 36–40.
  10. Ballabio E., Bersano A., Bresolin N., Candelise L. Monogenic vessel diseases related to ischemic stroke: a clinical approach. J. Cereb. Blood Flow Metab. 2007; 27 (10): 1649–1662.
  11. Beisiegel U., Weber W., Bengtsson-Olivecrona G. Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein. Proc. Natl. Acad. Sci. USA. 1991; 88 (19): 8342–8346.
  12. Bellenguez C., Bevan S., Gschwendtner A. et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat. Genet. 2012; 44 (3): 328–333.
  13. Bentley P., Peck G., Smeeth L. et al. Causal relationship of susceptibility genes to ischemic stroke: comparison to ischemic heart disease and biochemical determinants. PLoS One 2010; 5 (2): e9136.
  14. Bersano A., Ballabio E., Bresolin N., Candelise L. Genetic polymorphisms for the study of multifactorial stroke. Hum. Mutat. 2008; 29 (6):776–795.
  15. Bevan S., Traylor M., Adib-Samii P. et al. Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genome-wide associations. Stroke 2012; 43 (12): 3161–3167.
  16. Biffi A., Anderson C.D., Jagiella J.M. et al. APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study. Lancet. Neurol. 2011; 10 (8): 702–709.
  17. Biffi A., Sonni A., Anderson C.D. et al. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann. Neurol. 2010; 68 (6): 934–943.
  18. Bots M.L., Elwood P.C., Salonen J.T. et al. Level of fibrinogen and risk of fatal and non-fatal stroke. EUROSTROKE: a collaborative study among research centres in Europe. J. Epidemiol. Community Health 2002; 56: 114–118.
  19. Brass L.M., Isaacsohn J.L., Merikangas A.R. A study of twins and stroke. Stroke 1992; 23 (2): 221–223.
  20. Brouwers H.B., Biffi A., Ayres A.M. et al. Apolipoprotein E genotype predicts hematoma expansion in lobar intracerebral hemorrhage. Stroke 2012; 43 (6): 1490–1495.
  21. Casas J.P., Hingorani A.D., Bautista L.E., Sharma P. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch. Neurol. 2004; 61 (11): 1652–1661.
  22. Cattaneo M. Hyperhomocysteinemia, atherosclerosis and thrombosis. Thromb. Haemost. 1999; 81 (2): 165–176.
  23. Cope G., Golbang A., O'Shaughnessy K.M. WNK kinases and the control of blood pressure. Pharmacol. Ther. 2005; 106 (2): 221–231.
  24. Cronin S., Furie K.L., Kelly P.J. Dose-related association of MTHFR 677T allele with risk of ischemic stroke: evidence from a cumulative meta-analysis. Stroke 2005; 36 (7): 1581–1587.
  25. Dahabreh I.J., Kitsios G.D., Kent D.M., Trikalinos T.A. Paraoxonase 1 polymorphisms and ischemic stroke risk: A systematic review and meta-analysis. Genet. Med. 2010; 12 (10): 606–615.
  26. Dichgans M. Genetics of ischaemic stroke. Lancet. Neurol. 2007; 6 (2): 149–161.
  27. Dichgans M., Mayer M., Uttner I. et al. The phenotypic spectrum of CADASIL: clinical findings in 102 cases. Ann. Neurol. 1998; 44 (5): 731–739.
  28. Dziedzic T., Slowik A., Pera J., Szczudlik A. Interleukin 1 beta polymorphism (-511) and risk of stroke due to small vessel disease. Cerebrovasc. Dis. 2005; 20 (5): 299–303.
  29. Elbaz A., Poirier O., Canaple S. et al. The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction. Blood. 2000; 95 (2): 586–591.
  30. Flossmann E., Schulz U.G., Rothwell P.M. Systematic review of methods and results of studies of the genetic epidemiology of ischemic stroke. Stroke 2004; 35 (1): 212–227.
  31. Freiberg J.J., Tybjaerg-Hansen A., Sillesen H. et al. Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease. Arterioscler. Thromb. Vasc. Biol. 2008; 28 (5): 990–996.
  32. Girelli D., Russo C., Ferraresi P. et al. Polymorphisms in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease. N. Engl. J. Med. 2000; 343 (11): 774–780.
  33. Gonzalez-Conejero R., Lozano M.L., Rivera J. et al. Polymorphisms of platelet membrane glycoprotein Ib associated with arterial thrombotic disease. Blood 1998; 92 (8): 2771–2776.
  34. Gouveia L.O., Sobral J., Vicente A.M. et al. Replication of the CELSR1 association with ischemic stroke in a Portuguese case-control cohort. Atherosclerosis 2011; 217 (1): 260–262.
  35. Gretarsdottir S., Thorleifsson G., Manolescu A. et al. Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. Ann. Neurol. 2008; 64 (4): 402–409.
  36. Gschwendtner A., Bevan S., Cole J.W. et al. Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Ann. Neurol. 2009; 65 (5): 531–539.
  37. Gudbjartsson D.F., Holm H., Gretarsdottir S. et al. A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. Nat. Genet. 2009; 41 (8): 876–878.
  38. Guo J.M., Liu A.J., Su D.F. Genetics of stroke. Acta Pharmacol. 2010; 31 (9): 1055–1064.
  39. Haidari M., Hajilooi M., Rafiei A.R. et al. E-selectin genetic variation as a susceptibility factor for ischemic stroke. Cerebrovasc. Dis. 2009; 28 (1): 26–32.
  40. Hamedani A.G., Cole J.W., Mitchell B.D., Kittner S.J. Meta-analysis of factor V Leiden and ischemic stroke in young adults: the importance of case ascertainment. Stroke 2010; 41 (8): 1599–1603.
  41. Hassan A., Markus H.S. Genetics and ischaemic stroke. Brain 2000; 123 (9): 1784–1812.
  42. Hata J., Matsuda K., Ninomiya T. et al. Functional SNP in an Sp1- binding site of AGTRL1 gene is associated with susceptibility to brain infarction. Hum. Mol. Genet. 2007; 16 (6): 630–639.
  43. Helgadottir A., Gretarsdottir S., Thorleifsson G. et al. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism. J. Am. Coll. Cardiol. 2012; 60 (8): 722–729.
  44. Henskens L.H., Kroon A.A., van der Schouw Y.T. et al. Renin-angiotensin system and nitric oxide synthase gene polymorphisms in relation to stroke. Am. J. Hypertens. 2007; 20 (7): 764–770.
  45. Holliday E.G., Maguire J.M., Evans T.J. et al. Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nat. Genet. 2012; 44 (10): 1147–1151.
  46. Holmes M.V., Newcombe P., Hubacek J.A. et al. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet. 2011; 378 (9791): 584–594.
  47. Ikram M.A., Seshadri S., Bis J.C. et al. Genome wide association studies of stroke. N. Engl. J. Med. 2009; 360 (17): 1718–1728.
  48. Jerrard-Dunne P., Cloud G., Hassan A., Markus H.S. Evaluating the genetic component of ischemic stroke subtypes: a family history study. Stroke 2003; 34 (6): 1364–1369.
  49. Joutel A., Corpechot C., Ducros A. et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 1996; 383 (6602): 707–710.
  50. Kang S., Zhao X., Liu L. et al. Association of the C677T polymorphism in the MTHFR gene with hemorrhagic stroke: a meta-analysis. Genet. Test Mol. Biomarkers. 2013; 17 (5): 412–417.
  51. Kannel W.B., Benjamin E.J. Current perceptions of the epidemiology of atrial fibrillation. Cardiol. Clin. 2009; 27 (1): 13–24.
  52. Kilarski L.L., Achterberg S., DevanW.J. et al. Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12. Neurology 2014; 83 (8): 678–685.
  53. Kim H., Hysi P.G., Pawlikowska L. et al. Common variants in interleukin- 1-Beta gene are associated with intracranial hemorrhage and susceptibility to brain arteriovenous malformation. Cerebrovasc. Dis. 2009; 27 (2): 176–182.
  54. Kubo M., Hata J., Ninomiya T. et al. A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat. Genet. 2007; 39 (2): 212–217.
  55. Kucharska-Newton A.M., Monda K.L., Campbell S. et al. Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis 2011; 216 (1): 151–156.
  56. Laugesaar R., Kahre T., Kolk A. et al. Factor V Leiden and prothrombin 20210G>A [corrected] mutation and paediatric ischaemic stroke: a case-control study and two meta-analyses. Acta Paediatr. 2010; 99 (8): 1168–1174.
  57. Lemmens R., Buysschaert I., Geelen V. et al. The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology. Stroke 2010; 41 (9): 1850–1857.
  58. Liu H., Xia P., Liu M. et al. PON gene polymorphisms and ischaemic stroke: a systematic review and meta-analysis. Int. J. Stroke 2013; 8 (2): 111–123.
  59. Maguire J.M., Thakkinstian A., Sturm J. et al. Polymorphisms in platelet glycoprotein 1b alpha and factor VII and risk of ischemic stroke: a meta-analysis. Stroke 2008; 39 (6): 1710–1716.
  60. Martinelli I., Battaglioli T., Burgo I. et al. Oral contraceptive use, thrombophilia and their interaction in young women with ischemic stroke. Haematologica 2006; 91 (6): 844–847.
  61. Martiskainen M., Oksala N., Pohjasvaara T. et al. Beta-fibrinogen gene promoter A -455 allele associated with poor long term survival among 55-71 years old Caucasian women in Finnish stroke cohort. BMC Neurol. 2014; 14: 137.
  62. Martiskainen M., Pohjasvaara T., Mikkelsson J. et al. Fibrinogen gene promoter -455 A allele as a risk factor for lacunar stroke. Stroke 2003; 34 (4): 886–891.
  63. Matarin M., Brown W.M., Scholz S. et al. A genome-wide genotyping study in patients with ischaemic stroke: Initial analysis and data release. Lancet. Neurol. 2007; 6 (5): 414–420.
  64. Meschia J.F., Brott T.G., Brown R.D. Jr. Genetics of cerebrovascular disorders. Mayo Clin. Proc. 2005; 80 (1): 122–32.
  65. Murthy V., Julien P., Gagne C. Molecular pathobiology of the human lipoprotein lipase gene. Pharmacol. Ther. 1996; 70 (2): 101–135.
  66. Newton-Cheh C., Johnson T., Gateva V. et al. Genome-wide association study identifies eight loci associated with blood pressure. Nat. Genet. 2009; 41 (6): 666–676.
  67. Peck G., Smeeth L., Whittaker J. et al. The genetics of primary haemorrhagic stroke, subarachnoid haemorrhage and ruptured intracranial aneurysms in adults. PLoS One 2008; 3 (11): e3691.
  68. Pi Y., Zhang L., Yang Q. et al. Apolipoprotein A5 gene promoter region-1131T/C polymorphism is associated with risk of ischemic stroke and elevated triglyceride levels: a meta-analysis. Cerebrovasc. Dis. 2012; 33 (6): 558–565.
  69. Rao R., Tah V., Casas J.P. et al. Ischaemic stroke subtypes and their genetic basis: a comprehensive meta-analysis of small and large vessel stroke. Eur. Neurol. 2009; 61 (2): 76–86.
  70. Reiner A.P., Kumar P.N., Schwartz S.M. et al. Genetic variants of platelet glycoprotein receptors and risk of stroke in young women. Stroke 2000; 31 (7): 1628–1633.
  71. Rosendaal F.R., Siscovick D.S., Schwartz S.M. et al. Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. Blood 1997; 189 (8): 2817–2821.
  72. Rubattu S., Di A.E., Stanzione R. et al. Gene polymorphisms of the renin-angiotensin-aldosterone system and the risk of ischemic stroke: a role of the A1166C/AT1 gene variant. J. Hypertens. 2004; 22 (11): 2129–2134.
  73. Saidi S., Zammiti W., Slamia L.B. et al. Interaction of angiotensinconverting enzyme and apolipoprotein E gene polymorphisms in ischemic stroke involving large-vessel disease. J. Thromb. Thrombolysis 2009; 27 (1): 68–74.
  74. Salvi E., Kutalik Z., Glorioso N. et al. Genome-wide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase. Hypertension 2012; 59 (2): 248–255.
  75. Sarecka-Hujar B., Kopyta I., Pienczk-Reclawowicz K. et al. The TT genotype of methylenetetrahydrofolate reductase 677C>T polymorphism increases the susceptibility to pediatric ischemic stroke: metaanalysis of the 822 cases and 1,552 controls. Mol. Biol. Rep. 2012; 39 (8): 7957–7963.
  76. Schulz U.G., Flossmann E., Rothwell P.M. Heritability of ischemic stroke in relation to age, vascular risk factors, and subtypes of incident stroke in population-based studies. Stroke 2004; 35 (4): 819–824.
  77. Shiber J.R., Fontane E., Adewale A. A Stroke registry: hemorrhagic vs ischemic strokes. Am. J. Emerg. Med. 2010; 28 (3): 331–333.
  78. Siegerink B., Rosendaal F.R., Algra A. Genetic variation in fibrinogen; its relationship to fibrinogen levels and the risk of myocardial infarction and ischemic stroke. J. Thromb. Haemost. 2009; 7 (3): 385–390.
  79. Slooter A.J., Rosendaal F.R., Tanis B.C. at al. Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke. J. Thromb. Haemost. 2005; 3 (6): 1213–1217.
  80. Slowik A., Borratynska A., Turaj W. et al. Interleukin 1beta-511 C/T polymorphism and risk of aneurysmal subarachnoid haemorrhage. J. Neurol. Neurosurg. Psychiatry 2006; 77 (2): 279–280.
  81. Slowik A., Dziedzic T., Pera J. et al. Coagulation factor XIII VaI-34Leu polymorphism in patients with small vessel disease or primary intracerebral hemorrhage. Cerebrovasc. Dis. 2005; 19 (3): 165–170.
  82. Slowik A., Dziedzic T., Turaj W. et al. A2 alelle of GpIIIa gene is a risk factor for stroke caused by large-vessel disease in males. Stroke 2004; 35 (7): 1589–1593.
  83. Stankovic S., Majkic-Singh N. Genetic aspects of ischemic stroke: coagulation, homocysteine, and lipoprotein metabolism as potential risk factors. Crit. Rev. Clin. Lab. Sci. 2010; 47 (2): 72–123.
  84. Szolnoki Z., Havasi V., Talian G. et al. Angiotensin II type-1 receptor A1166C polymorphism is associated with increased risk of ischemic stroke in hypertensive smokers. J. Mol. Neurosci. 2006; 28 (3): 285–290.
  85. Tao H.M., Chen G.Z. Endothelial NO synthase gene polymorphisms and risk of ischemic stroke: a meta-analysis. Neurosci. Res. 2009; 64 (3): 311–316.
  86. Touzé E., Rothwell P.M. Sex differences in heritability of ischemic stroke: a systematic review and meta-analysis. Stroke 2008; 39 (1): 16–23.
  87. Traylor M., Farrall M., Holliday E.G. et al. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. Lancet. Neurol. 2012; 11 (11): 951–962.
  88. Tybjaerg-Hansen A., Agerholm-Larsen B., Humphries S.E. et al. A common mutation (G-455–> A) in the beta-fibrinogen promoter is an independent predictor of plasma fibrinogen, but not of ischemic heart disease. A study of 9,127 individuals based on the Copenhagen City
  89. Heart Study. J. Clin. Invest. 1997; 99 (12): 3034–3039.
  90. Van Cott E.M., Laposata M. Laboratory evaluation of hypercoagula ble states. Hematol. Oncol. Clin. North. Am. 1998; 12 (6): 1141–1166.
  91. Volcik K.A., Ballantyne C.M., Hoogeveen R. et al. Intercellular adhesion molecule-1 G241R polymorphism predicts risk of incident ischemic stroke: Atherosclerosis Risk in Communities study. Stroke 2010; 41 (5): 1038–1040.
  92. Wang C., Sun T., Li H. et al. Lipoprotein lipase Ser447Ter polymorphism associated with the risk of ischemic stroke: a meta-analysis. Thromb. Res. 2011; 128 (5): 107–112.
  93. Wang W.Y., Zee R.Y., Morris B.J. Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension. Clin. Genet. 1997; 51 (1): 31–34.
  94. Wang W.Y.S., Barratt B.J., Clayton D.G., Todd J.A. Genome-wide association studies: theoretical and practical concerns. Nat. Rev. Genet. 2005; 6 (2): 109–118.
  95. Wang X., Cheng S., Brophy V.H. et al. A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients. Stroke 2009; 40 (3): 683–695.
  96. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447 (7145): 661–678.
  97. Whisnant J.P. Modeling of risk factors for ischemic stroke. The Willis Lecture. Stroke 1997; 28 (9): 1840–1844.
  98. Xin X.Y., Song Y.Y., Ma J.F. et al. Gene polymorphisms and risk of adult early-onset ischemic stroke: A meta-analysis. Thromb. Res. 2009; 124 (5): 619–624.
  99. Yamada Y., Fuku N., Tanaka M. et al. Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study. Atherosclerosis 2009; 207 (1): 144–149.
  100. Ye F., Jin X.Q., Chen G.H. et al. Polymorphisms of interleukin-1 and interleukin-6 genes on the risk of ischemic stroke in a meta-analysis. Gene 2012; 499 (1): 61–69.
  101. Yoon D., Park S.K., Kang D. et al. Meta-analysis of homogeneous subgroups reveals association between PDE4D gene variants and ischemic stroke. Neuroepidemiology 2011; 36 (4): 213–22.
  102. Zakai N.A., Lange L., Longstreth W.T. et al. Association of coagulationrelated and inflammation-related genes and factor VIIc levels with stroke: the Cardiovascular Health Study. J. Thromb. Haemost. 2011; 9 (2): 267–274.
  103. Zhang Z., Xu G., Liu D. et al. Angiotensin-converting enzyme insertion/ deletion polymorphism contributes to ischemic stroke risk: a metaanalysis of 50 case-control studies. PLoS One 2012; 7 (10): e46495.
  104. Zhao X., Jiang H. Quantitative assessment of the association between MTHFR C677T polymorphism and hemorrhagic stroke risk. Mol. Biol. Rep. 2013; 40 (1): 573–578.

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML

© Korchagin V.I., Mironov K.O., Dribnokhodova O.P., Maxsimova M.Y., Illarioshkin S.N., Tanashyn M.M., Platonov A.E., Shipulin G.A., Raskurazhev A.A., Piradov M.A., 2016

Creative Commons License
Эта статья доступна по лицензии Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77-83204 от 12.05.2022.


Данный сайт использует cookie-файлы

Продолжая использовать наш сайт, вы даете согласие на обработку файлов cookie, которые обеспечивают правильную работу сайта.

О куки-файлах