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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">urmj</journal-id><journal-title-group><journal-title xml:lang="ru">Уральский медицинский журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Ural Medical Journal</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2949-4389</issn><publisher><publisher-name>Ural State Medical University</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.52420/umj.24.1.108</article-id><article-id custom-type="edn" pub-id-type="custom">ZSJFLR</article-id><article-id custom-type="elpub" pub-id-type="custom">urmj-1729</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Оригинальные статьи | Original articles</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Original articles</subject></subj-group></article-categories><title-group><article-title>Клинико-патогенетические факторы риска инсульта у пациентов с неуточненным (криптогенным) патогенетическим вариантом ишемического инсульта согласно критериям TOAST</article-title><trans-title-group xml:lang="en"><trans-title>Clinical and Genetic Risk Factors in Patients with an Unspecified (Cryptogenic) Pathogenetic Variant According to the TOAST Criteria</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7210-945X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Галкин</surname><given-names>С. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Galkin</surname><given-names>S. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сергей Сергеевич Галкин — кандидат медицинских наук, ассистент кафедры неврологии, нейрохирургии и медицинской генетики, институт нейронаук и нейротехнологий;</p><p>невролог отделения для больных с острым нарушением мозгового кровообращения</p><p>Москва</p></bio><bio xml:lang="en"><p>Sergei S. Galkin — Candidate of Sciences (Medicine), Assistant of the Department of Neurology, Neurosurgery and Medical Genetics, Institute of Neuroscience and Neurotechnology;</p><p>Neurologist of the Department for Patients with Acute Cerebrovascular Accident</p><p>Moscow</p></bio><email xlink:type="simple">ser.62@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4532-4434</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Анисимов</surname><given-names>К. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Anisimov</surname><given-names>K. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кирилл Владимирович Анисимов — кандидат медицинских наук, врач рентгенэндоваскулярных диагностики и лечения;</p><p>невролог, научный сотрудник института цереброваскулярной патологии и инсульта</p><p>Москва</p></bio><bio xml:lang="en"><p>Kirill V. Anisimov — Candidate of Sciences (Medicine), Endovascular Radiologist;</p><p>Neurologist, Researcher of the Institute of Cerebrovascular Pathology and Stroke</p><p>Moscow</p></bio><email xlink:type="simple">anisimov.org@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3322-9357</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гунченко</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Gunchenko</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Анастасия Сергеевна Гунченко — кандидат медицинских наук, невролог</p><p>Москва</p></bio><bio xml:lang="en"><p>Anastasia S. Gunchenko — Candidate of Sciences (Medicine), Neurologist</p><p>Moscow</p></bio><email xlink:type="simple">dr.nevrolog@list.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8434-5916</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Иконникова</surname><given-names>А. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Ikonnikova</surname><given-names>A. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Анна Юрьевна Иконникова — кандидат медицинских наук, ведущий инженер лаборатории биологических микрочипов</p><p>Москва</p></bio><bio xml:lang="en"><p>Anna Yu. Ikonnikova — Candidate of Sciences (Medicine), Leading Engineer of the Laboratory of Biological Microarrays</p><p>Moscow</p></bio><email xlink:type="simple">anyuik@gmail.com</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0007-6570-7786</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шапкин</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Shapkin</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Михаил Алексеевич Шапкин — анестезиолог-реаниматолог, заведующий отделением реанимации и интенсивной терапии для больных с острым нарушением мозгового кровообращения, региональный сосудистый центр</p><p>Москва</p></bio><bio xml:lang="en"><p>Mikhail A. Shapkin — Anesthesiologist-Resuscitator, Head of the Intensive Care Unit for Patients with Acute Cerebrovascular Accident, Regional Vascular Center</p><p>Moscow</p></bio><email xlink:type="simple">Mihailshapkin6230@gmail.com</email><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9209-9121</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Анисимова</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Anisimova</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Анастасия Вячеславовна Анисимова — доктор медицинских наук, профессор, профессор кафедры неврологии, нейрохирургии и медицинской генетики, институт нейронаук и нейротехнологий;</p><p>невролог отделения реанимации и интенсивной терапии для больных с острым нарушением мозгового кровообращения, региональный сосудистый центр</p><p>Москва</p></bio><bio xml:lang="en"><p>Anastasia V. Anisimova — Doctor of Sciences (Medicine), Professor, Professor of the Department of Neurology, Neurosurgery and Medical Genetics, Institute of Neuroscience and Neurotechnology;</p><p>Neurologist Intensive Care Unit for Patients with Acute Cerebrovascular Accident, Regional Vascular Center</p><p>Moscow</p></bio><email xlink:type="simple">gssh@mail.ru</email><xref ref-type="aff" rid="aff-6"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2642-4202</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Наседкина</surname><given-names>Т. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Nasedkina</surname><given-names>T. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Татьяна Васильевна Наседкина — доктор биологических наук, профессор, ведущий научный сотрудник лаборатории биологических микрочипов</p><p>Москва</p></bio><bio xml:lang="en"><p>Tatyana V. Nasedkina — Doctor of Sciences (Biology), Professor, Leading Researcher of the Laboratory of Biological Microarrays</p><p>Moscow</p></bio><email xlink:type="simple">tanased06@rambler.ru</email><xref ref-type="aff" rid="aff-4"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Российский национальный исследовательский медицинский университет имени Н. И. Пирогова;&#13;
Городская клиническая больница имени И. В. Давыдовского</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Pirogov Russian National Research Medical University;&#13;
I. V. Davydovsky City Clinical Hospital</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Городская клиническая больница имени И. В. Давыдовского;&#13;
Федеральный центр мозга и нейротехнологий</institution><country>Россия</country></aff><aff xml:lang="en"><institution>I. V. Davydovsky City Clinical Hospital;&#13;
Federal Center for Brain and Neurotechnology</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Главное бюро медико-социальной экспертизы по г. Москве</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Main Bureau of Medical and Social Expertise in Moscow</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>Институт молекулярной биологии имени В. А. Энгельгардта Российской академии наук</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Engelhardt Institute of Molecular Biology, Russian Academy of Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru"><institution>Городская клиническая больница № 1 имени Н. И. Пирогова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Pirogov City Clinical Hospital No. 1</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-6"><aff xml:lang="ru"><institution>Российский национальный исследовательский медицинский университет имени Н. И. Пирогова;&#13;
Городская клиническая больница № 1 имени Н. И. Пирогова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Pirogov Russian National Research Medical University;&#13;
Pirogov City Clinical Hospital No. 1</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>03</day><month>03</month><year>2025</year></pub-date><volume>24</volume><issue>1</issue><elocation-id>108–122</elocation-id><permissions><copyright-statement>Copyright &amp;#x00A9; Галкин С.С., Анисимов К.В., Гунченко А.С., Иконникова А.Ю., Шапкин М.А., Анисимова А.В., Наседкина Т.В., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Галкин С.С., Анисимов К.В., Гунченко А.С., Иконникова А.Ю., Шапкин М.А., Анисимова А.В., Наседкина Т.В.</copyright-holder><copyright-holder xml:lang="en">Galkin S.S., Anisimov K.V., Gunchenko A.S., Ikonnikova A.Y., Shapkin M.A., Anisimova A.V., Nasedkina T.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.umjusmu.ru/jour/article/view/1729">https://www.umjusmu.ru/jour/article/view/1729</self-uri><abstract><p>Обоснование. Как показывают последни е научные исследования, для криптогенного ишемического инсульта (ИИ) характерна гетерогенность этиопатогенетических механизмов, что указывает на актуальность поиска потенциальных факторов риска развития криптогенного ИИ, в т. ч. клинико-генетических.Цель исследования — исследовать ассоциации генетических маркеров, влияющих на спонтанную и индуцированную агрегацию тромбоцитов (АТ), клинико-лабораторных показателей у пациентов с неуточненным характером ИИ согласно критериям TOAST для выявления потенциальных клинико-генетических факторов риска и более глубокого понимания патогенетических механизмов заболевания.Материалы и методы. В исследование включено 196 пациентов с неуточненным патогенетическим вариантом ИИ. Исследованы ассоциации полиморфизмов генов ITGB3, GPIba, TBXA2R, ITGA2, PLA2G7, HMOX1, PTGS1, PTGS2, ADRA2A, ABCB1, PEAR1 и межгенной области 9p21.3 с клинико-лабораторными параметрами.Результаты. Носительство генотипа G/G rs1062535 ITGA2 ассоциировалось с достоверно более низкими показателями спонтанной АТ по сравнению с пациентами с генотипами G/A+A/A. У пациентов с генотипом С/С PLA2G7 уровень спонтанной АТ (ОП %) являлся значимо (p = 0,041) более низким по сравнению с пациентами с генотипами T/C+T/T. У пациентов с генотипом С/С rs4523 TBXA2R определялся достоверно (p &lt; 0,050) ниже показатель АТ, инду цированной аденозиндифосфатом, по сравнению с пациентами с генотипами C/T+T/T. У пациентов с генотипом С/С rs5918 ITGB3 достоверно более низкий показатель АТ, индуцированной адреналином, по сравнению с пациентами с генотипами T/T+T/C. У пациентов с генотипом A/A rs1062535 ITGA2 уровень АТ, индуцированной ристомицином, достоверно (p &lt; 0,050) выше по сравнению с пациентами с генотипами G/G+G/A.Заключение. Носительство генотипов G/A+A/A ITGA2, T/C+T/T PLA2G7, C/T+T/T TBXA2R, A/A ITGA2 может быть использовано как потенциальный маркер течения ИИ неуточненного патогенетического варианта.</p></abstract><trans-abstract xml:lang="en"><p>Background. Recent studies emphasize the heterogeneity of cryptogenic ischemic stroke (IS), highlighting the importance of identifying clinical and genetic risk factors.Objective. This study explores the associations between genetic markers affecting spontaneous and induced platelet aggregation (PA) and clinical parameters in patients with unspecified IS according to TOAST criteria, aiming to uncover potential risk factors and understand the disease’s pathogenetic mechanisms.Materials and methods. The study included 196 patients diagnosed with unspecified ischemic stroke. We examined the associations of various gene polymorphisms (ITGB3, GPIba, TBXA2R, ITGA2, PLA2G7, HMOX1, PTGS1, PTGS2, ADRA2A, ABCB1, PEAR1) with clinical and laboratory parameters.Results. The G/G rs1062535 ITGA2 genotype was linked to significantly lower spontaneous aggregation rates than the G/A+A/A genotypes. Patients with the C/C PLA2G7 genotype had a significantly lower spontaneous aggregation level (SA %) compared to T/C+T/T genotypes (p = 0.041). The C/C genotype rs4523 TBXA2R showed a significantly lower ADP-induced PA rate compared to C/T+T/T (p &lt; 0.050). Similarly, those with the C/C genotype rs5918 ITGB3 had significantly lower adrenaline-induced PA rates compared to T/T+T/C. Conversely, patients with the A/A genotype rs1062535 ITGA2 exhibited significantly higher ristomycin-induced AT rates than G/G+G/A genotypes.Conclusion. The G/A+A/A ITGA2, T/C+T/T PLA2G7, C/T+T/T TBXA2R, and A/A ITGA2 genotypes may serve as potential markers for the course of unspecified ischemic stroke.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>ишемический инсульт</kwd><kwd>ген</kwd><kwd>агрегация тромбоцитов</kwd><kwd>ген ITGA2</kwd><kwd>ген PLA2G7</kwd><kwd>ген TBXA2R</kwd><kwd>ген ITGA2</kwd></kwd-group><kwd-group xml:lang="en"><kwd>ischemic stroke</kwd><kwd>gene</kwd><kwd>platelet aggregation</kwd><kwd>ITGA2 gene</kwd><kwd>PLA2G7 gene</kwd><kwd>TBXA2R gene</kwd><kwd>ITGA2 gene</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Ramazanov GR, Magomedov TA, Khamidova LT, Rybal’ko NV, Petrikov SS, Shamalov NA. Etiology of cryptogenic stroke. Russian Sklifosovsky Journal “Emergency Medical Care”. 2019;8(3):302–314. DOI: https://doi.org/10.23934/2223-9022-2019-8-3-302-314.</mixed-citation><mixed-citation xml:lang="en">Ramazanov GR, Magomedov TA, Khamidova LT, Rybal’ko NV, Petrikov SS, Shamalov NA. Etiology of cryptogenic stroke. Russian Sklifosovsky Journal “Emergency Medical Care”. 2019;8(3):302–314. DOI: https://doi.org/10.23934/2223-9022-2019-8-3-302-314.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic stroke of undetermined source: A systematic review and clinical update. Stroke. 2017;48(4):867–872. DOI: https://doi.org/10.1161/strokeaha.116.016414.</mixed-citation><mixed-citation xml:lang="en">Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic stroke of undetermined source: A systematic review and clinical update. Stroke. 2017;48(4):867–872. DOI: https://doi.org/10.1161/strokeaha.116.016414.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Vinogradov OI, Yablonskiy MA, Kuznetsov AN. Embolic stroke of undetermined source. S. S. Korsakov Journal of Neurology and Psychiatry. 2020;120(12–2):42–48. (In Russ.). DOI: https://doi.org/10.17116/jnevro202012012242.</mixed-citation><mixed-citation xml:lang="en">Vinogradov OI, Yablonskiy MA, Kuznetsov AN. Embolic stroke of undetermined source. S. S. Korsakov Journal of Neurology and Psychiatry. 2020;120(12–2):42–48. (In Russ.). DOI: https://doi.org/10.17116/jnevro202012012242.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Diener HC, Easton JD, Hart RG, Kasner S, Kamel H, Ntaios G. Review and update of the concept of embolic stroke of undetermined source. Nature Reviews Neurology. 2022;18(8):455–465. DOI: https://doi.org/10.1038/s41582-022-00663-4.</mixed-citation><mixed-citation xml:lang="en">Diener HC, Easton JD, Hart RG, Kasner S, Kamel H, Ntaios G. Review and update of the concept of embolic stroke of undetermined source. Nature Reviews Neurology. 2022;18(8):455–465. DOI: https://doi.org/10.1038/s41582-022-00663-4.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Diener HC, Bernstein R, Hart R. Secondary stroke prevention in cryptogenic stroke and embolic stroke of undetermined source (ESUS). Current Neurology and Neuroscience Reports. 2017;17(9):64. DOI: https://doi.org/10.1007/s11910-017-0775-5.</mixed-citation><mixed-citation xml:lang="en">Diener HC, Bernstein R, Hart R. Secondary stroke prevention in cryptogenic stroke and embolic stroke of undetermined source (ESUS). Current Neurology and Neuroscience Reports. 2017;17(9):64. DOI: https://doi.org/10.1007/s11910-017-0775-5.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41. DOI: https://doi.org/10.1161/01.str.24.1.35.</mixed-citation><mixed-citation xml:lang="en">Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41. DOI: https://doi.org/10.1161/01.str.24.1.35.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20(7):864–870. DOI: https://doi.org/10.1161/01.str.20.7.864.</mixed-citation><mixed-citation xml:lang="en">Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20(7):864–870. DOI: https://doi.org/10.1161/01.str.20.7.864.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Gschwendtner A, Bevan S, Cole JW, Plourde A, Matarin M, Ross-Adams H, et al. Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Annals of Neurology. 2009;65(5):531–539. DOI: https://doi.org/10.1002/ana.21590.</mixed-citation><mixed-citation xml:lang="en">Gschwendtner A, Bevan S, Cole JW, Plourde A, Matarin M, Ross-Adams H, et al. Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Annals of Neurology. 2009;65(5):531–539. DOI: https://doi.org/10.1002/ana.21590.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Gryadunov DA, Zimenko DV, Mikhailovich VM, Nasedkina TV, Dement’eva EI, Rubina AY, et al. Technology of hydrogel biochips and its application in medical laboratory diagnostics. Medical Alphabet. 2012; 1(2):58–59. (In Russ.). EDN: https://elibrary.ru/OYPVWX</mixed-citation><mixed-citation xml:lang="en">Gryadunov DA, Zimenko DV, Mikhailovich VM, Nasedkina TV, Dement’eva EI, Rubina AY, et al. Technology of hydrogel biochips and its application in medical laboratory diagnostics. Medical Alphabet. 2012; 1(2):58–59. (In Russ.). EDN: https://elibrary.ru/OYPVWX</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Bentley P, Peck G, Smeeth L, Whittaker J, Sharma P. Causal relationship of susceptibility genes to ischemic stroke: Comparison to ischemic heart disease and biochemical determinants. PLoS One. 2010;5(2): e9136. DOI: https://doi.org/10.1371/journal.pone.0009136.</mixed-citation><mixed-citation xml:lang="en">Bentley P, Peck G, Smeeth L, Whittaker J, Sharma P. Causal relationship of susceptibility genes to ischemic stroke: Comparison to ischemic heart disease and biochemical determinants. PLoS One. 2010;5(2): e9136. DOI: https://doi.org/10.1371/journal.pone.0009136.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Liang X, Zhou Y, Li S. Association of TBXA2R, P2Y12 and ADD1 genes polymorphisms with ischemic stroke susceptibility: A metaanalysis. Clinical and Investigative Medicine. 2020;43(3): E33–E43. DOI: https://doi.org/10.25011/cim.v43i3.34597.</mixed-citation><mixed-citation xml:lang="en">Liang X, Zhou Y, Li S. Association of TBXA2R, P2Y12 and ADD1 genes polymorphisms with ischemic stroke susceptibility: A metaanalysis. Clinical and Investigative Medicine. 2020;43(3): E33–E43. DOI: https://doi.org/10.25011/cim.v43i3.34597.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Meschia JF, Nalls M, Matarin M, Brott TG, Brown RD Jr, Hardy J, et al. Siblings with ischemic stroke study investigators. Siblings with ischemic stroke study: Results of a genome-wide scan for stroke loci. Stroke. 2011;42(10):2726–2732. DOI: https://doi.org/10.1161/STROKEAHA.111.620484.</mixed-citation><mixed-citation xml:lang="en">Meschia JF, Nalls M, Matarin M, Brott TG, Brown RD Jr, Hardy J, et al. Siblings with ischemic stroke study investigators. Siblings with ischemic stroke study: Results of a genome-wide scan for stroke loci. Stroke. 2011;42(10):2726–2732. DOI: https://doi.org/10.1161/STROKEAHA.111.620484.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Liu X, Zhu RX, Tian YL, Li Q, Li L, Deng SM, et al. Association of PLA2G7 gene polymorphisms with ischemic stroke in northern Chinese Han population. Clinical Biochemistry. 2014;47(6):404–408. DOI: https://doi.org/10.1016/j.clinbiochem.2014.01.010.</mixed-citation><mixed-citation xml:lang="en">Liu X, Zhu RX, Tian YL, Li Q, Li L, Deng SM, et al. Association of PLA2G7 gene polymorphisms with ischemic stroke in northern Chinese Han population. Clinical Biochemistry. 2014;47(6):404–408. DOI: https://doi.org/10.1016/j.clinbiochem.2014.01.010.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Batra N, De Souza C, Batra J, Raetz AG, Yu AM. The HMOX1 pathway as a promising target for the treatment and prevention of SARS-CoV-2 of 2019 (COVID-19). International Journal of Molecular Sciences. 2020;21(17):6412. DOI: https://doi.org/10.3390/ijms21176412.</mixed-citation><mixed-citation xml:lang="en">Batra N, De Souza C, Batra J, Raetz AG, Yu AM. The HMOX1 pathway as a promising target for the treatment and prevention of SARS-CoV-2 of 2019 (COVID-19). International Journal of Molecular Sciences. 2020;21(17):6412. DOI: https://doi.org/10.3390/ijms21176412.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Cai H, Cai B, Sun L, Zhang H, Zhou S, Cao L, et al. Association between PTGS1 polymorphisms and functional outcomes in Chinese patients with stroke during aspirin therapy: Interaction with smoking. Journal of the Neurological Sciences. 2017;376:211–215. DOI: https://doi.org/10.1016/j.jns.2017.03.014.</mixed-citation><mixed-citation xml:lang="en">Cai H, Cai B, Sun L, Zhang H, Zhou S, Cao L, et al. Association between PTGS1 polymorphisms and functional outcomes in Chinese patients with stroke during aspirin therapy: Interaction with smoking. Journal of the Neurological Sciences. 2017;376:211–215. DOI: https://doi.org/10.1016/j.jns.2017.03.014.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Oh SH, Min KT, Jeon YJ, Kim MH, Kim OJ, Shin BS, et al. Association between common genetic variants of α2A-, α2B-, and α2C-adrenergic receptors and ischemic stroke. Clinical Neurology and Neurosurgery. 2013;115(1):26–31. DOI: https://doi.org/10.1016/j.clineuro.2012.04.002.</mixed-citation><mixed-citation xml:lang="en">Oh SH, Min KT, Jeon YJ, Kim MH, Kim OJ, Shin BS, et al. Association between common genetic variants of α2A-, α2B-, and α2C-adrenergic receptors and ischemic stroke. Clinical Neurology and Neurosurgery. 2013;115(1):26–31. DOI: https://doi.org/10.1016/j.clineuro.2012.04.002.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Kim YO, Kim SY, Yun DH, Lee SW. Association between ABCB1 polymorphisms and ischemic stroke in Korean population. Experimental Neurobiology. 2012;21(4):164–171. DOI: https://doi.org/10.5607/en.2012.21.4.164.</mixed-citation><mixed-citation xml:lang="en">Kim YO, Kim SY, Yun DH, Lee SW. Association between ABCB1 polymorphisms and ischemic stroke in Korean population. Experimental Neurobiology. 2012;21(4):164–171. DOI: https://doi.org/10.5607/en.2012.21.4.164.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Li Z, Jiang H, Ding Y, Zhang D, Zhang X, Xue J, et al. Platelet endothelial aggregation receptor 1 polymorphism is associated with functional outcome in small-artery occlusion stroke patients treated with aspirin. Frontiers in Cardiovascular Medicine. 2021;8:664012. DOI: https://doi.org/10.3389/fcvm.2021.664012.</mixed-citation><mixed-citation xml:lang="en">Li Z, Jiang H, Ding Y, Zhang D, Zhang X, Xue J, et al. Platelet endothelial aggregation receptor 1 polymorphism is associated with functional outcome in small-artery occlusion stroke patients treated with aspirin. Frontiers in Cardiovascular Medicine. 2021;8:664012. DOI: https://doi.org/10.3389/fcvm.2021.664012.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Gryadunov DA, Shaskol’skiy BL, Nasedkina TV, Rubina AY, Zasedatelev AS. Technology of hydrogel biochips of IMB RAS: 30 years later. Acta Naturae. 2018;10(4):4–18. (In Russ.). DOI: https://doi.org/10.32607/20758251-2018-10-4-4-18.</mixed-citation><mixed-citation xml:lang="en">Gryadunov DA, Shaskol’skiy BL, Nasedkina TV, Rubina AY, Zasedatelev AS. Technology of hydrogel biochips of IMB RAS: 30 years later. Acta Naturae. 2018;10(4):4–18. (In Russ.). DOI: https://doi.org/10.32607/20758251-2018-10-4-4-18.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Jackson SP. Arterial thrombosis — insidious, unpredictable and deadly. Nature Medicine. 2011;17: 1423–1436. DOI: https://doi.org/10.1038/nm.2515.</mixed-citation><mixed-citation xml:lang="en">Jackson SP. Arterial thrombosis — insidious, unpredictable and deadly. Nature Medicine. 2011;17: 1423–1436. DOI: https://doi.org/10.1038/nm.2515.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Kunicki TJ, Orchekowski R, Annis D, Honda Y. Variability of integrin alpha 2 beta 1 activity on human platelets. Blood. 1993;82(9):2693–2703. DOI: https://doi.org/10.1182/blood.V82.9.2693.2693.</mixed-citation><mixed-citation xml:lang="en">Kunicki TJ, Orchekowski R, Annis D, Honda Y. Variability of integrin alpha 2 beta 1 activity on human platelets. Blood. 1993;82(9):2693–2703. DOI: https://doi.org/10.1182/blood.V82.9.2693.2693.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Liu H, Wang Y, Zheng J, Li G, Chen T, Lei J, et al. Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis. International Journal of Stroke. 2017;12(1):46–70. DOI: https://doi.org/10.1177/1747493016672085.</mixed-citation><mixed-citation xml:lang="en">Liu H, Wang Y, Zheng J, Li G, Chen T, Lei J, et al. Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis. International Journal of Stroke. 2017;12(1):46–70. DOI: https://doi.org/10.1177/1747493016672085.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Bell R, Collier DA, Rice SQ, Roberts GW, MacPhee CH, Kerwin RW, et al. Systematic screening of the LDL-PLA2 gene for polymorphic variants and case‐control analysis in schizophrenia. Biochemical and Biophysical Research Communications. 1997;241(3):630–635. DOI: https://doi.org/10.1006/bbrc.1997.7741.</mixed-citation><mixed-citation xml:lang="en">Bell R, Collier DA, Rice SQ, Roberts GW, MacPhee CH, Kerwin RW, et al. Systematic screening of the LDL-PLA2 gene for polymorphic variants and case‐control analysis in schizophrenia. Biochemical and Biophysical Research Communications. 1997;241(3):630–635. DOI: https://doi.org/10.1006/bbrc.1997.7741.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Gregson JM, Freitag DF, Surendran P, Stitziel NO, Chowdhury R, Burgess S, et al. Genetic invalidation of Lp‐PLA2 as a therapeutic target: Large‐scale study of five functional Lp‐PLA2‐lowering alleles. European Journal of Preventive Cardiology. 2017;24(5):492–504. DOI: https://doi.org/10.1177/2047487316682186.</mixed-citation><mixed-citation xml:lang="en">Gregson JM, Freitag DF, Surendran P, Stitziel NO, Chowdhury R, Burgess S, et al. Genetic invalidation of Lp‐PLA2 as a therapeutic target: Large‐scale study of five functional Lp‐PLA2‐lowering alleles. European Journal of Preventive Cardiology. 2017;24(5):492–504. DOI: https://doi.org/10.1177/2047487316682186.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Casas JP, Ninio E, Panayiotou A, Palmen J, Cooper JA, Ricketts SL, et al. PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10,494 cases and 15,624 controls of European ancestry. Circulation. 2010;121(21):2284–2293. DOI: https://doi.org/10.1161/CIRCULATIONAHA.109.923383.</mixed-citation><mixed-citation xml:lang="en">Casas JP, Ninio E, Panayiotou A, Palmen J, Cooper JA, Ricketts SL, et al. PLA2G7 genotype, lipoprotein-associated phospholipase A2 activity, and coronary heart disease risk in 10,494 cases and 15,624 controls of European ancestry. Circulation. 2010;121(21):2284–2293. DOI: https://doi.org/10.1161/CIRCULATIONAHA.109.923383.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Grallert H, Dupuis J, Bis JC, Dehghan A, Barbalic M, Baumert J, et al. Eight genetic loci associated with variation in lipoprotein‐associated phospholipase A2 mass and activity and coronary heart disease: Meta‐analysis of genome‐wide association studies from five community‐based studies. European Heart Journal. 2012; 33(2):238–251. DOI: https://doi.org/10.1093/eurheartj/ehr372.</mixed-citation><mixed-citation xml:lang="en">Grallert H, Dupuis J, Bis JC, Dehghan A, Barbalic M, Baumert J, et al. Eight genetic loci associated with variation in lipoprotein‐associated phospholipase A2 mass and activity and coronary heart disease: Meta‐analysis of genome‐wide association studies from five community‐based studies. European Heart Journal. 2012; 33(2):238–251. DOI: https://doi.org/10.1093/eurheartj/ehr372.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Chae JS, Kwak JH, Kim M, Shin KH, Lee SH, Jeong TS, et al. Effects of A379V variant of the Lp-PLA2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans. Journal of Thrombosis and Thrombolysis. 2014;38(4):477–484. DOI: https://doi.org/10.1007/s11239-014-1074-5.</mixed-citation><mixed-citation xml:lang="en">Chae JS, Kwak JH, Kim M, Shin KH, Lee SH, Jeong TS, et al. Effects of A379V variant of the Lp-PLA2 gene on Lp-PLA2 activity and markers of oxidative stress and endothelial function in Koreans. Journal of Thrombosis and Thrombolysis. 2014;38(4):477–484. DOI: https://doi.org/10.1007/s11239-014-1074-5.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Qi Y, Zhao D, Jia Z, Wang W, Wang M, Sun J, et al. A previously unreported impact of a PLA2G7 gene polymorphism on the plasma levels of lipoprotein‐associated phospholipase A2 activity and mass. Scientific Reports. 2016;6:37465. DOI: https://doi.org/10.1038/srep37465.</mixed-citation><mixed-citation xml:lang="en">Qi Y, Zhao D, Jia Z, Wang W, Wang M, Sun J, et al. A previously unreported impact of a PLA2G7 gene polymorphism on the plasma levels of lipoprotein‐associated phospholipase A2 activity and mass. Scientific Reports. 2016;6:37465. DOI: https://doi.org/10.1038/srep37465.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Yeo A, Li L, Warren L, Aponte J, Fraser D, King K, et al. Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib. PLoS One. 2017;12(7): e0182115. DOI: https://doi.org/10.1371/journal.pone.0182115.</mixed-citation><mixed-citation xml:lang="en">Yeo A, Li L, Warren L, Aponte J, Fraser D, King K, et al. Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib. PLoS One. 2017;12(7): e0182115. DOI: https://doi.org/10.1371/journal.pone.0182115.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Liu PY, Li YH, Wu HL, Chao TH, Tsai LM, Lin LJ, et al. Platelet‐activating factor‐acetylhydrolase A379V (exon 11) gene polymorphism is an independent and functional risk factor for premature myocardial infarction. Journal of Thrombosis and Haemostasis. 2006;4(5):1023–1028. DOI: https://doi.org/10.1111/j.1538-7836.2006.01895.x.</mixed-citation><mixed-citation xml:lang="en">Liu PY, Li YH, Wu HL, Chao TH, Tsai LM, Lin LJ, et al. Platelet‐activating factor‐acetylhydrolase A379V (exon 11) gene polymorphism is an independent and functional risk factor for premature myocardial infarction. Journal of Thrombosis and Haemostasis. 2006;4(5):1023–1028. DOI: https://doi.org/10.1111/j.1538-7836.2006.01895.x.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Wang Z, Gao F, Men J, Yang J, Modi P, Wei M. Polymorphisms and high on-aspirin platelet reactivity after off-pump coronary artery bypass grafting. Scandinavian Cardiovascular Journal. 2013;47(4):194–199. DOI: https://doi.org/10.3109/14017431.2013.800640.</mixed-citation><mixed-citation xml:lang="en">Wang Z, Gao F, Men J, Yang J, Modi P, Wei M. Polymorphisms and high on-aspirin platelet reactivity after off-pump coronary artery bypass grafting. Scandinavian Cardiovascular Journal. 2013;47(4):194–199. DOI: https://doi.org/10.3109/14017431.2013.800640.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Undas A, Brummel K, Musial J, Mann KG, Szczeklik . Pl (A2) polymorphism of beta (3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury. Circulation. 2001;27;104(22):2666–2672. DOI: https://doi.org/10.1161/hc4701.099787.</mixed-citation><mixed-citation xml:lang="en">Undas A, Brummel K, Musial J, Mann KG, Szczeklik . Pl (A2) polymorphism of beta (3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury. Circulation. 2001;27;104(22):2666–2672. DOI: https://doi.org/10.1161/hc4701.099787.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
