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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">ymj</journal-id><journal-title-group><journal-title xml:lang="ru">Якутский медицинский журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Yakut Medical Journal</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1813-1905</issn><issn pub-type="epub">2312-1017</issn><publisher><publisher-name>ЯНЦ КМП</publisher-name></publisher></journal-meta><article-meta><article-id custom-type="elpub" pub-id-type="custom">ymj-1417</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>Статьи</subject></subj-group></article-categories><title-group><article-title>Статус метилирования генов контроля клеточного цикла в тканях сонных артерий у больных атеросклерозом</article-title><trans-title-group xml:lang="en"><trans-title>Methylation Status of the Cell Cycle Control-Associated Genes in the Carotid Artery Tissue of Atherosclerotic patients</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Назаренко</surname><given-names>М. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Nazarenko</surname><given-names>M. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Назаренко Мария Сергеевна – н.с. </p></bio><bio xml:lang="en"><p>Maria S. Nazarenko, Ph.D </p><p>10 Ushaika Embankment, Tomsk, 634050 </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Марков</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Markov</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Марков Антон Владимирович – аспирант </p></bio><bio xml:lang="en"><p>Anton V. Markov </p><p>10 Ushaika Embankment, Tomsk, 634050 </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Королёва</surname><given-names>Ю. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Koroleva</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Королёва Юлия Александровна – ординатор </p></bio><bio xml:lang="en"><p> Iuliia A. Koroleva ccccccc</p><p> 10 Ushaika Embankment, Tomsk, 634050 </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лебедев</surname><given-names>И. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Lebedev</surname><given-names>I. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Лебедев Игорь Николаевич – д.б.н., зав. лаб. </p></bio><bio xml:lang="en"><p> Igor N. Lebedev, Ph.D. </p><p> 10 Ushaika Embankment, Tomsk, 634050 </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Слепцов</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Sleptcov</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Слепцов Алексей Анатольевич – аспирант </p></bio><bio xml:lang="en"><p> Alexei A. Sleptcov </p><p> 10 Ushaika Embankment, Tomsk, 634050 </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Фролов</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Frolov</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Фролов Алексей Витальевич – к.м.н., н.с. НИИ комплексных проблем сердечнососудистых заболеваний СО РАМН  </p></bio><bio xml:lang="en"><p> Alexey V. Frolov, Ph.D. </p><p> 6 Sosnovy Blvd, Kemerovo, 650002 </p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Барбараш</surname><given-names>О. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Barbarash</surname><given-names>O. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Барбараш Ольга Леонидовна – д.м.н., проф., директор НИИ комплексных проблем сердечно-сосудистых заболеваний СО РАМН </p></bio><bio xml:lang="en"><p> Olga L. Barbarash, Ph.D., MD </p><p> 6 Sosnovy Blvd, Kemerovo, 650002 </p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пузырёв</surname><given-names>В. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Puzyrev</surname><given-names>V. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Пузырёв Валерий Павлович – акад. РАМН, проф., директор </p></bio><bio xml:lang="en"><p> Valery P. Puzyrev Ph.D., MD </p><p> 10 Ushaika Embankment, Tomsk, 634050 </p></bio><xref ref-type="aff" rid="aff-4"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>НИИ медицинской генетики СО РАМН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute of Medical Genetics, Siberian Branch, Russian Academy of Medical Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>НИИ комплексных проблем сердечнососудистых заболеваний СО РАМН  </institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute for Complex Problems of Cardiovascular Diseases, Siberian Branch, Russian Academy of Medical Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>НИИ комплексных проблем сердечно-сосудистых заболеваний СО РАМН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute for Complex Problems of Cardiovascular Diseases, Siberian Branch, Russian Academy of Medical Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>РАМН</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute of Medical Genetics, Siberian Branch, Russian Academy of Medical Sciences</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>14</day><month>09</month><year>2025</year></pub-date><volume>0</volume><issue>2</issue><fpage>61</fpage><lpage>63</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Назаренко М.С., Марков А.В., Королёва Ю.А., Лебедев И.Н., Слепцов А.А., Фролов А.В., Барбараш О.Л., Пузырёв В.П., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Назаренко М.С., Марков А.В., Королёва Ю.А., Лебедев И.Н., Слепцов А.А., Фролов А.В., Барбараш О.Л., Пузырёв В.П.</copyright-holder><copyright-holder xml:lang="en">Nazarenko M.S., Markov A.V., Koroleva I.A., Lebedev I.N., Sleptcov A.A., Frolov A.V., Barbarash O.L., Puzyrev V.P.</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://ymj.elpub.ru/jour/article/view/1417">https://ymj.elpub.ru/jour/article/view/1417</self-uri><abstract><p>Проведен анализ статуса метилирования промоторов и первых экзонов генов CDKN2A (p16INK4a, p14ARF), CDKN2B (p15INK4b) и RB1 в 120 образцах сонных артерий с применением двух различных технологий: метилчувствительной полимеразной цепной реакции (МЧ-ПЦР) и метилспецифичной ПЦР (МС-ПЦР). Метилирование ДНК не было выявлено в выраженных атеросклеротических бляшках или прилежащих макроскопически неизменённых тканях сосудистой стенки тех же самых больных. Установлено, что статус метилирования генов CDKN2A, CDKN2B и RB1 не может быть использован в качестве маркера атеросклероза в сонных артериях человека.</p></abstract><trans-abstract xml:lang="en"><sec><title>Objective</title><p>Objective: We tested the hypothesis that the aberrant methylation of the promoters and first exons of CDKN2A (p16INK4a, p14ARF), CDKN2B (p15INK4b) and RB1 genes was associated with carotid atherosclerosis.</p></sec><sec><title>Methods and results</title><p>Methods and results: The DNA methylation status of these cell cycle control-associated genes was analysed in 120 samples of carotid arteries using two different techniques: methylationsensitive polymerase chain reaction (MS-PCR) and methylation-specific PCR (MSP-PCR). DNA methylation was not detected in advanced atherosclerotic plaques or nearby macroscopically intact tissues of the vascular wall from the same patients.</p></sec><sec><title>Conclusion</title><p>Conclusion: The methylation status of CDKN2A, CDKN2B and RB1 genes does not appear to be a marker of human carotid atherosclerosis.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>метилирование ДНК</kwd><kwd>атеросклероз</kwd><kwd>CDKN2A</kwd><kwd>CDKN2B</kwd><kwd>RB1</kwd></kwd-group><kwd-group xml:lang="en"><kwd>DNA methylation</kwd><kwd>atherosclerosis</kwd><kwd>CDKN2A</kwd><kwd>CDKN2B</kwd><kwd>RB1</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование поддержано грантом Российского фонда фундаментальных исследований (№ 10-04-00674a) и ФЦП «Научные и педагогические кадры инновационной России» (№8062).</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">Аномальное метилирование некоторых генов-супрессоров при спорадическом раке молочной железы / В.В. Землякова, А.И. Жевлова, В.В. Стрельников [и др.] // Молекулярная биология. – 2003. – Т.37, №4. – С. 696-703.</mixed-citation><mixed-citation xml:lang="en">Abnormal methylation of some tumor suppressor genes at sporadic breast cancer / V. V. Zemliakova, A.I. Zhevlova, V.V. Strel’nikov [et al.] // Mol. Biol. – 2003. – V. 37, № 4. – P. 696- 703.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Amatya V.J. Methylation of p14(ARF) gene in meningiomas and its correlation to the p53 expression and mutation / V.J. Amatya, Y. Takeshima, K. Inai // Mod. Pathol. – 2004. – V. 17, № 6. – P. 705-710.</mixed-citation><mixed-citation xml:lang="en">Amatya V.J. Methylation of p14(ARF) gene in meningiomas and its correlation to the p53 expression and mutation / V.J. Amatya, Y. Takeshima, K. Inai // Mod. Pathol. – 2004. – V. 17, № 6. – P. 705-710.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Baccarelli A. Cardiovascular epigenetics: basic concepts and results from animal and human studies / A. Baccarelli, M. Rienstra, E.J. Benjamin // Circ. Cardiovasc. Genet. – 2010. – V. 3. – № 6. – P. 567-573.</mixed-citation><mixed-citation xml:lang="en">Baccarelli A. Cardiovascular epigenetics: basic concepts and results from animal and human studies / A. Baccarelli, M. Rienstra, E.J. Benjamin // Circ. Cardiovasc. Genet. – 2010. – V. 3. – № 6. – P. 567-573.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Control of cell proliferation in atherosclerosis: insights from animal models and human studies / J. J. Fuster, P. Fernandez, H. Gonzalez-Navarro [et al.] // Cardiovasc. Res. – 2010. – V. 86. – № 2. – P. 254-264.</mixed-citation><mixed-citation xml:lang="en">Control of cell proliferation in atherosclerosis: insights from animal models and human studies / J. J. Fuster, P. Fernandez, H. Gonzalez-Navarro [et al.] // Cardiovasc. Res. – 2010. – V. 86. – № 2. – P. 254-264.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">DNA hypomethylation and methyltransferase expression in atherosclerotic lesions / M.O. Hiltunen, M.P. Turunen, T. P. Rutanen [et al.] // Vasc. Med. – 2002. – V. 7. – № 1. – P. 5-11.</mixed-citation><mixed-citation xml:lang="en">DNA hypomethylation and methyltransferase expression in atherosclerotic lesions / M.O. Hiltunen, M.P. Turunen, T. P. Rutanen [et al.] // Vasc. Med. – 2002. – V. 7. – № 1. – P. 5-11.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Epigenetics and atherosclerosis / M.P. Turunen, E. Aavik, S. Yla-Herttuala // Biochim. Biophys. Acta. – 2009. – V. 1790, № 9. – P. 886- 891.</mixed-citation><mixed-citation xml:lang="en">Epigenetics and atherosclerosis / M.P. Turunen, E. Aavik, S. Yla-Herttuala // Biochim. Biophys. Acta. – 2009. – V. 1790, № 9. – P. 886- 891.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence / J. Kim, J.Y. Kim, K.S. Song [et al.] // Biochim. Biophys. Acta. – 2007. – V. 1772, № 1. – P. 72-80.</mixed-citation><mixed-citation xml:lang="en">Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence / J. Kim, J.Y. Kim, K.S. Song [et al.] // Biochim. Biophys. Acta. – 2007. – V. 1772, № 1. – P. 72-80.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Extensive demethylation of normally hypermethylated CpG islands occurs in human atherosclerotic arteries / S.A. Castillo-Diaz, M.E. Garay-Sevilla, M.A. Hernandez-Gonzalez [et al.] // Int. J. Mol. Med. – 2010. – V. 26, № 5. – P. 691-700.</mixed-citation><mixed-citation xml:lang="en">Extensive demethylation of normally hypermethylated CpG islands occurs in human atherosclerotic arteries / S.A. Castillo-Diaz, M.E. Garay-Sevilla, M.A. Hernandez-Gonzalez [et al.] // Int. J. Mol. Med. – 2010. – V. 26, № 5. – P. 691-700.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Holdt L.M. Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations / L.M. Holdt, D. Teupser // Arterioscler. Thromb. Vasc. Biol. – 2012. – V. 32, № 2. – P. 196-206.</mixed-citation><mixed-citation xml:lang="en">Holdt L.M. Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations / L.M. Holdt, D. Teupser // Arterioscler. Thromb. Vasc. Biol. – 2012. – V. 32, № 2. – P. 196-206.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice / L.S. Boesten, A.S. Zadelaar, A. Nieuwkoop [et al.] // FASEB. J. – 2006. – V. 20, № 7. – P. 953-955.</mixed-citation><mixed-citation xml:lang="en">Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice / L.S. Boesten, A.S. Zadelaar, A. Nieuwkoop [et al.] // FASEB. J. – 2006. – V. 20, № 7. – P. 953-955.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system / W.S. Post, P.J. Goldschmidt-Clermont, C. C. Wilhide [et al.] // Cardiovasc. Res. – 1999. – V. 43, № 4. – P. 985- 991.</mixed-citation><mixed-citation xml:lang="en">Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system / W.S. Post, P.J. Goldschmidt-Clermont, C. C. Wilhide [et al.] // Cardiovasc. Res. – 1999. – V. 43, № 4. – P. 985- 991.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands / J.G. Herman, J.R. Graff, S. Myohanen [et al.] // Proc. Natl. Acad. Sci. U.S.A. – 1996. – V. 93, №18. – P.9821-9826.</mixed-citation><mixed-citation xml:lang="en">Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands / J.G. Herman, J.R. Graff, S. Myohanen [et al.] // Proc. Natl. Acad. Sci. U.S.A. – 1996. – V. 93, №18. – P.9821-9826.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis / H. GonzalezNavarro, Y.N. Abu Nabah [et al.] // J. Am. Coll. Cardiol. – 2010. – V. 55, № 20. – P. 2258-2268.</mixed-citation><mixed-citation xml:lang="en">p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis / H. GonzalezNavarro, Y.N. Abu Nabah [et al.] // J. Am. Coll. Cardiol. – 2010. – V. 55, № 20. – P. 2258-2268.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Tissue factor pathway inhibitor-2 gene methylation is associated with low expression in carotid atherosclerotic plaques / C. Zawadzki, N. Chatelain, M. Delestre [et al.] // Atherosclerosis. – 2009. – V. 204, № 2. – P. e4-14.</mixed-citation><mixed-citation xml:lang="en">Tissue factor pathway inhibitor-2 gene methylation is associated with low expression in carotid atherosclerotic plaques / C. Zawadzki, N. Chatelain, M. Delestre [et al.] // Atherosclerosis. – 2009. – V. 204, № 2. – P. e4-14.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Inactivation of monocarboxylate transporter MCT3 by DNA methylation in atherosclerosis / S. Zhu, P. J. Goldschmidt-Clermont, C. Dong // Circulation. – 2005. – V. 112, № 9. – P. 1353- 1361.</mixed-citation><mixed-citation xml:lang="en">Inactivation of monocarboxylate transporter MCT3 by DNA methylation in atherosclerosis / S. Zhu, P. J. Goldschmidt-Clermont, C. Dong // Circulation. – 2005. – V. 112, № 9. – P. 1353- 1361.</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>
