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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">ateroskleroz</journal-id><journal-title-group><journal-title xml:lang="ru">Атеросклероз</journal-title><trans-title-group xml:lang="en"><trans-title>Ateroscleroz</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2078-256X</issn><issn pub-type="epub">2949-3633</issn><publisher><publisher-name>НИИТПМ-филиал ИЦиГ СО РАН</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.52727/2078-256X-2024-20-2-121-135</article-id><article-id custom-type="elpub" pub-id-type="custom">ateroskleroz-1049</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</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>Ассоциация вариантов генов АРОЕ, СЕТР и хромосомного региона 9Р21.3 с ишемической болезнью сердца, инфарктом миокарда и острой сердечной недостаточностью</article-title><trans-title-group xml:lang="en"><trans-title>Association of variants of the APOE, CETP genes and the 9P21.3 chromosomal region with coronary heart disease, myocardial infarction and acute heart failure</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3999-8501</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Семаев</surname><given-names>С. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Semaev</surname><given-names>S. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сергей Евгеньевич Семаев, младший научный сотрудник</p><p>лаборатория молекулярно-генетических исследований терапевтических заболеваний; сектор изучения моногенных форм распространенных заболеваний человека</p><p>630089; ул. Бориса Богаткова, 175/1; 630090; пр. Академика Лаврентьева, 10; Новосибирск</p></bio><bio xml:lang="en"><p>Sergey E. Semaev, junior researcher</p><p>laboratory of molecular genetic investigations of therapeutic diseases; laboratory of the study of monogenic forms of common human diseases</p><p>630089; 175/1, Boris Bogatkov str.; 630090; 10, Academician Lavrentiev av.; Novosibirsk</p></bio><email xlink:type="simple">sse281985@yandex.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/0000-0001-9270-9188</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Щербакова</surname><given-names>Л. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Shcherbakova</surname><given-names>L. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Лилия Валерьевна Щербакова, старший научный сотрудник</p><p>лаборатория клинико-популяционных и профилактических исследований терапевтических и эндокринных заболеваний</p><p>630089; ул. Бориса Богаткова, 175/1; Новосибирск</p></bio><bio xml:lang="en"><p>Liliya V. Shcherbakova, researcher</p><p>laboratory of clinical-populational and prophylactic studies on internal and endocrine diseases</p><p>630089; 175/1, Boris Bogatkov str.; Novosibirsk</p></bio><email xlink:type="simple">scherbakovalv@bionet.nsc.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9371-2178</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Орлов</surname><given-names>П. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Orlov</surname><given-names>P. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Павел Сергеевич Орлов, научный сотрудник, младший научный сотрудник</p><p>лаборатория молекулярно-генетических исследований терапевтических заболеваний; лаборатория молекулярной генетики человека</p><p>630089; ул. Бориса Богаткова, 175/1; 630090; пр. Академика Лаврентьева, 10; Новосибирск</p></bio><bio xml:lang="en"><p>Pavel S. Orlov, researcher</p><p>laboratory of the molecular genetic investigations of the therapeutic diseases; laboratory of human molecular genetics</p><p>630089; 175/1, Boris Bogatkov str.; 630090; 10, Academician Lavrentiev av.; Novosibirsk</p></bio><email xlink:type="simple">orlovpavel186@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0403-545X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Иванощук</surname><given-names>Д. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Ivanoshchuk</surname><given-names>D. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Динара Евгеньевна Иванощук, научный сотрудник, младший научный сотрудник</p><p>лаборатория молекулярно-генетических исследований терапевтических заболеваний; лаборатория молекулярной генетики человека</p><p>630089; ул. Бориса Богаткова, 175/1; 630090; пр. Академика Лаврентьева, 10; Новосибирск</p></bio><bio xml:lang="en"><p>Dinara E. Ivanoshchuk, researcher, junior researcher</p><p>laboratory of the molecular genetic investigations of the therapeutic diseases; laboratory of human molecular genetics</p><p>630089; 175/1, Boris Bogatkov str.; 630090; 10, Academician Lavrentiev av.; Novosibirsk</p></bio><email xlink:type="simple">dinara2084@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/0000-0001-6539-0466</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Малютина</surname><given-names>С. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Malyutina</surname><given-names>S. K.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Софья Константиновна Малютина, д-р мед. наук, проф., главный научный сотрудник, зав. лабораторией</p><p>лаборатория этиопатогенеза и клиники внутренних заболеваний</p><p>630089; ул. Бориса Богаткова, 175/1; Новосибирск</p></bio><bio xml:lang="en"><p>Sofia K. Malyutina, PhD, MD, ScD, Professor, head of the laboratory</p><p>laboratory of etiopathogenesis and clinics of internal diseases</p><p>630089; 175/1, Boris Bogatkov str.; Novosibirsk</p></bio><email xlink:type="simple">smalyutina@hotmail.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/0000-0001-5701-7856</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гафаров</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Gafarov</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Валерий Васильевич Гафаров, д-р мед. наук, проф., главный научный сотрудник, зав. лабораторией</p><p>лаборатория психологических и социологических проблем терапевтических заболеваний</p><p>630089; ул. Бориса Богаткова, 175/1; Новосибирск</p></bio><bio xml:lang="en"><p>Valery V. Gafarov, PhD, MD, ScD, Professor, head of the laboratory</p><p>laboratory psychological and sociological problems</p><p>630089; 175/1, Boris Bogatkov str.; Novosibirsk</p></bio><email xlink:type="simple">valery.gafarov@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/0000-0001-9425-413X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Воевода</surname><given-names>М. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Voevoda</surname><given-names>M. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Михаил Иванович Воевода, д-р мед. наук, проф., академик РАН, научный консультант</p><p>630090; пр. Академика Лаврентьева, 10; Новосибирск</p></bio><bio xml:lang="en"><p>Mikhail I. Voevoda, a member of the Russian Academy of Sciences, PhD, MD, ScD, Professor, Scientific consultant</p><p>630090; 10, Academician Lavrentiev av.; Novosibirsk</p></bio><email xlink:type="simple">mvoevoda@ya.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/0000-0002-4936-8362</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рагино</surname><given-names>Ю. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Ragino</surname><given-names>Yu. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Юлия Игоревна Рагино, д-р мед. наук, проф., член-корреспондент РАН, главный научный сотрудник, руководитель</p><p>630089; ул. Бориса Богаткова, 175/1; Новосибирск</p></bio><bio xml:lang="en"><p>Yulia I. Ragino, MD, professor, corresponding member of the Russian Academy of Sciences, head</p><p>630089; 175/1, Boris Bogatkov str.; Novosibirsk</p></bio><email xlink:type="simple">ragino@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6108-1025</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шахтшнейдер</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Shakhtshneider</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Елена Владимировна Шахтшнейдер, канд. мед. наук, ведущий научный сотрудник, зав. сектором</p><p>сектор изучения моногенных форм распространенных заболеваний человека</p><p>630089; ул. Бориса Богаткова, 175/1; 630090; пр. Академика Лаврентьева, 10; Новосибирск</p></bio><bio xml:lang="en"><p>Elena V. Shakhtshneider, candidate of medical sciences, MD, leader researcher, head of the laboratory</p><p>laboratory of the molecular genetic investigations of therapeutic disease; laboratory of the study of monogenic forms of human common disease</p><p>630089; 175/1, Boris Bogatkov str.; 630090; 10, Academician Lavrentiev av.; Novosibirsk</p></bio><email xlink:type="simple">2117409@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Научно-исследовательский институт терапии и профилактической медицины – филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»; Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»<country>Россия</country></aff><aff xml:lang="en">Research Institute of Internal and Preventive Medicine –&#13;
Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences; Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Научно-исследовательский институт терапии и профилактической медицины – филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»<country>Россия</country></aff><aff xml:lang="en">Research Institute of Internal and Preventive Medicine –&#13;
Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru">Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»<country>Россия</country></aff><aff xml:lang="en">Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>03</day><month>07</month><year>2024</year></pub-date><volume>20</volume><issue>2</issue><fpage>121</fpage><lpage>135</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Семаев С.Е., Щербакова Л.В., Орлов П.С., Иванощук Д.Е., Малютина С.К., Гафаров В.В., Воевода М.И., Рагино Ю.И., Шахтшнейдер Е.В., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Семаев С.Е., Щербакова Л.В., Орлов П.С., Иванощук Д.Е., Малютина С.К., Гафаров В.В., Воевода М.И., Рагино Ю.И., Шахтшнейдер Е.В.</copyright-holder><copyright-holder xml:lang="en">Semaev S.E., Shcherbakova L.V., Orlov P.S., Ivanoshchuk D.E., Malyutina S.K., Gafarov V.V., Voevoda M.I., Ragino Y.I., Shakhtshneider E.V.</copyright-holder><license 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://ateroskleroz.elpub.ru/jour/article/view/1049">https://ateroskleroz.elpub.ru/jour/article/view/1049</self-uri><abstract><p>   Актуальной задачей для системы здравоохранения служит выявление слоев населения, наиболее предрасположенных к сердечно-сосудистым заболеваниям (ССЗ) атеросклеротического генеза. Стратификация риска – важный компонент выбора стратегии ведения как больных ССЗ, так и лиц с факторами риска. Индивидуальный риск неблагоприятного сердечно-сосудистого исхода определяется генетическими факторами в дополнение к факторам образа жизни.</p><p>   Цель работы – изучить ассоциацию вариантов генов АРОЕ, СЕТР и хромосомного региона 9p21.3 с ишемической болезнью сердца (ИБС), инфарктом миокарда (ИМ) и острой сердечной недостаточностью (ОСН) в выборке жителей г. Новосибирска (Западная Сибирь).</p><sec><title>   Материал и методы</title><p>   Материал и методы. Выборка: 2516 участников проекта HAPIEE (57,5 ± 0,2 года, соотношение мужчин и женщин 45 : 55). Выбор вариантов АРОЕ, СЕТР и хромосомного региона 9p21.3 был обусловлен их значимой ассоциацией с ССЗ по данным ряда исследований и метаанализов. Генотипирование rs708272, rs429358 и rs7412 проводили методом ПЦР в режиме реального времени с помощью реагентов TaqMan, генотипирование rs1333049 – с использованием коммерческого набора KASP.</p></sec><sec><title>   Результаты</title><p>   Результаты. Определена ассоциация аллеля С rs1333049 с повышенным риском развития ИБС, ИМ и ОСН в подгруппе мужчин (р = 0,008) и в общей группе (р = 0,002). В общей группе частота развития ИБС, ИМ и ОСН была статистически значимо ниже у носителей аллеля G (отношение шансов 0,748, 95 %-й доверительный интервал 0,606–0,924, р = 0,007). Мы подтвердили ассоциацию генотипа ɛ2/ɛ4 гена АРОЕ с ИБС, ИМ и ОСН в подгруппе мужчин (р = 0,007) и в общей группе (р = 0,009). В подгруппе женщин с ИБС, ИМ и ОСН был ассоциирован генотип ɛ2/ɛ2 (р &lt; 0,0001), в то время как у носителей генотипа ɛ3/ɛ3 частота развития ИБС, ИМ и ОСН была статистически значимо ниже (отношение шансов 0,675, 95 %-й доверительный интервал 0,509–0,894, р = 0,006).</p></sec><sec><title>   Заключение</title><p>   Заключение. Показана ассоциация rs1333049 хромосомного региона 9p21.3, rs429358 и rs7412 гена APOE с риском развития ИБС, ИМ и ОСН в выборке жителей г. Новосибирска. Данные варианты могут быть рекомендованы для включения в генетический рискометр ССЗ.</p></sec></abstract><trans-abstract xml:lang="en"><p>   A relevant task for the healthcare system is to identify the groups most predisposed to cardiovascular diseases (CVD) of atherosclerotic genesis. Risk stratification is an important component of choosing a management strategy for both CVD patients and those with risk factors. The individual risk of an unfavorable cardiovascular outcome is determined by genetic factors in addition to lifestyle factors.</p><p>   The aim of the work was to examine the association of variants of the APOE, CETP and chromosomal region 9p21.3 with coronary heart disease (CHD), myocardial infarction (MI) and acute heart failure (ACF) in a sample of residents of Novosibirsk.</p><sec><title>   Material and methods</title><p>   Material and methods. Sample: 2516 participants of the HAPIEE project (57.5 ± 0.2 years old, male to female ratio 45:55). The choice of the variants of the APOE, CETP and the chromosomal region 9p21.3 was due to their significant association with CVD according to several studies and meta-analyses. Genotyping of rs708272, rs429358 and rs7412 was performed by Real-Time PCR using TaqMan reagents; genotyping of rs1333049 was performed using a commercial KASP kit.</p></sec><sec><title>   Results</title><p>   Results. Allele C of rs1333049 was associated with an increased risk of CHD, MI and AHF in the subgroup of men (p = 0,008) and in the general group (p = 0,002). In the general group, the incidence of CHD, MI and AHF was significantly lower in carriers of the G allele (odds ratio 0.748, 95 % confidence interval 0.606–0.924, p = 0.007). We confirmed the association of the ɛ2/ɛ4 genotype of the APOE gene with CHD, MI and AHF among males (p = 0.007) and in the whole study sample (p = 0.009). In the women subgroup the genotype ɛ2/ɛ2 (p &lt; 0.0001) was associated with CHD, MI and AHF, while in carriers of the genotype ɛ3/ɛ3, the incidence of CHD, MI and AHF was significantly lower (odds ratio 0.675, 95 % confidence interval 0.509–0.894, p = 0,006).</p></sec><sec><title>   Conclusions</title><p>   Conclusions. This work shows the association of rs1333049 of chromosomal region 9p21.3 and rs429358&amp;rs7412 of the APOE gene with the risk of CHD, MI and AHF in a sample of residents of Novosibirsk. These variants may be recommended for inclusion into a genetic risk score.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>АРОЕ</kwd><kwd>СЕТР</kwd><kwd>rs1333049</kwd><kwd>ишемическая болезнь сердца</kwd><kwd>инфаркт миокарда</kwd><kwd>острая сердечная недостаточность</kwd><kwd>атеросклеротические сердечно-сосудистые заболевания</kwd></kwd-group><kwd-group xml:lang="en"><kwd>APOE</kwd><kwd>CETP</kwd><kwd>rs1333049</kwd><kwd>coronary heart disease</kwd><kwd>myocardial infarction</kwd><kwd>acute heart failure</kwd><kwd>atherosclerotic cardiovascular diseases</kwd></kwd-group><funding-group xml:lang="ru"><funding-statement>Работа выполнена в рамках темы Государственного задания FWNR-2024-0004</funding-statement></funding-group><funding-group xml:lang="en"><funding-statement>This research was conducted within the framework of the main topic in state assignment FWNR-2024-0004</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Nielsen S.H., Mouton A.J., DeLeon-Pennell K.Y., Genovese F., Karsdal M., Lindsey M. 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