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<article 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" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Annals of the Russian academy of medical sciences</journal-id><journal-title-group><journal-title xml:lang="en">Annals of the Russian academy of medical sciences</journal-title><trans-title-group xml:lang="ru"><trans-title>Вестник Российской академии медицинских наук</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0869-6047</issn><issn publication-format="electronic">2414-3545</issn><publisher><publisher-name xml:lang="en">"Paediatrician" Publishers LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">1108</article-id><article-id pub-id-type="doi">10.15690/vramn1108</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>STATE OF MEDICAL SCIENCES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>СОСТОЯНИЕ МЕДИЦИНСКОЙ НАУКИ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Personalized Medicine</article-title><trans-title-group xml:lang="ru"><trans-title>Персонализированная медицина</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8175-7886</contrib-id><name-alternatives><name xml:lang="en"><surname>Dedov</surname><given-names>Ivan I.</given-names></name><name xml:lang="ru"><surname>Дедов</surname><given-names>Иван Иванович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Professor</p><p>11 Dm.Ulyanova street, Moscow, 117036</p><p>SPIN-cod: 5873-2280</p></bio><bio xml:lang="ru"><p>Доктор медицинских наук, профессор, академик РАН.</p><p>117036, Москва, ул. Дм. Ульянова, д. 11</p><p> </p><p>SPIN-код: 5873-2280</p></bio><email>dedov@endocrincentr.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Endocrinology Research Centre</institution></aff><aff><institution xml:lang="ru">Национальный медицинский исследовательский центр эндокринологии</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">I.M. Sechenov First Moscow State Medical University (Sechenov University)</institution></aff><aff><institution xml:lang="ru">Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет), Москва Российская Федерация</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2019-04-04" publication-format="electronic"><day>04</day><month>04</month><year>2019</year></pub-date><volume>74</volume><issue>1</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>61</fpage><lpage>70</lpage><history><date date-type="received" iso-8601-date="2019-02-26"><day>26</day><month>02</month><year>2019</year></date><date date-type="accepted" iso-8601-date="2019-02-26"><day>26</day><month>02</month><year>2019</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2019, "Paediatrician" Publishers LLC</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2019, Издательство "Педиатръ"</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="en">"Paediatrician" Publishers LLC</copyright-holder><copyright-holder xml:lang="ru">Издательство "Педиатръ"</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2020-04-04"/></permissions><self-uri xlink:href="https://vestnikramn.spr-journal.ru/jour/article/view/1108">https://vestnikramn.spr-journal.ru/jour/article/view/1108</self-uri><abstract xml:lang="en"><p>Evidence-based medicine at the end of the 20th century saved many lives, allowing us to reliably screen out pseudoscientific and dangerous methods. The medical community has gained access to weighted “standards” for treating common diseases. Unfortunately, this algorithmic approach pays for the breadth of coverage with low specificity of recommendations. In this article, the necessity and timeliness of the next step - the transition from broad clinical generalizations to working with the individual characteristics of the patient - are substantiated. The discussion opens with a forced criticism of the current state of clinical medicine, which suffers from economic inefficiency and low accuracy of pharmacotherapy. According to the FDA reference agency, up to 75% of patients do not respond to medications, which is very alarming and requires a change in the dominant paradigm in medicine. Next, we turn to the scientific and technological prerequisites of personalized healing, focusing on the achievements of molecular genetics and the value of genetic counseling. We also deal with issues of genome-wide sequencing and rapidly developing post-genomic methods. Taking into account international experience, we consider organizational and methodological difficulties, as well as ways to overcome them on the way to personalization of medicine. Key points of the article are illustrated by case reports from the clinical practice of the Endocrinology research centre (Moscow).</p></abstract><trans-abstract xml:lang="ru"><p>Внедрение доказательной медицины в конце XX века сохранило множество жизней, позволив надежно отсеивать лженаучные и опасные методы. Врачебное сообщество получило доступ к взвешенным «стандартам» лечения распространенных заболеваний. К сожалению, за широту охвата этот алгоритмический подход платит низкой специфичностью рекомендаций. В данной работе обоснованы необходимость и своевременность следующего шага ― перехода от широких клинических обобщений к работе с индивидуальными особенностями пациента. Обсуждение открывается вынужденной критикой современного состояния клинической медицины, страдающей от экономической неэффективности и низкой точности фармакотерапии. По данным референсного агентства FDA, до 75% пациентов не отвечает на медикаменты, что вселяет большую тревогу и требует смены главенствующей парадигмы. Далее мы переходим к научно-технологическим предпосылкам персонализированного врачевания, уделяя особое внимание достижениям молекулярной генетики и ценности генетического консультирования. Мы также касаемся вопросов полногеномного секвенирования и стремительно развивающихся постгеномных методов. С учетом международного опыта мы рассматриваем организационные и методологические трудности, а также способы их преодоления на пути к персонализации медицины. Ключевые тезисы иллюстрируются примерами из клинической практики НМИЦ эндокринологии.</p></trans-abstract><kwd-group xml:lang="en"><kwd>personalized medicine</kwd><kwd>translational medicine</kwd><kwd>evidence based medicine</kwd><kwd>healthcare</kwd><kwd>socially significant diseases</kwd><kwd>endocrinology</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>персонализированная медицина</kwd><kwd>трансляционная медицина</kwd><kwd>доказательная медицина</kwd><kwd>здравоохранение</kwd><kwd>социально-значимые заболевания</kwd><kwd>эндокринология</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Sur RL, Dahm P. History of evidence-based medicine. Indian J Urol. 2011;27(4):487–489. doi: 10.4103/0970-1591.91438.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>fda.gov [Internet]. Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development. 2013 [cited 2018 Feb 20]. Available from: http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/PersonalizedMedicine/UCM372421.pdf.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Jain KK. Textbook of personalized medicine. 2nd ed. New York: Springer; 2009. doi: 10.1007/978-1-4419-0769-1.</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>ncbi.nlm.nih.gov [Internet]. NCBI. Literature. PubMed Central (PMC) [cited 2018 Feb 20]. Available from: https://www.ncbi.nlm.nih.gov/pmc/?term=personalized%20medicine.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Schleidgen S, Klingler C, Bertram T, et al. What is personalized medicine: sharpening a vague term based on a systematic literature review. BMC Med Ethics. 2013;14:55. doi: 10.1186/1472-6939-14-55.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>O’Donnell JC. Personalized medicine and the role of health economics and outcomes research: issues, applications, emerging trends, and future research. Value Health. 2013;16(6 Suppl):S1–S3. doi: 10.1016/j.jval.2013.06.004.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Report of the USA President’s Council of Advisors on Science and Technology. Priorities for Personalized Medicine [Internet]. 2008 [cited 2018 Feb 20]. Available from: http://oncotherapy.us/pdf/PM.Priorities.pdf.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Terkola R, Antoñanzas F, Postma M. Economic evaluation of personalized medicine: a call for real-world data. Eur J Health Econ. 2017;18(9):1065–1067. doi: 10.1007/s10198-017-0890-x.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Abrahams E, Silver M. The case for personalized medicine. J Diabetes Sci Technol. 2009;3(4):680–684. doi: 10.1177/193229680900300411.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Дедов И.И., Терехин С.А., Калашников В.Ю., и др. Одномоментная эндовакулярная реваскуляризация почки, нижней конечности и эндоваскулярная реконструкция аневризмы брюшной аорты у пациента с сахарным диабетом 2 типа // Ангиология и сосудистая хирургия. ― 2012. ― T.18. ― №3 ― C. 51–56.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>genome.gov [Internet]. National Human Genome Research Institute. The Cost of Sequencing a Human Genome [cited 2018 Feb 20]. Available from: https://www.genome.gov/27565109/the-cost-of-sequencing-a-human-genome/.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>genome.gov [Internet]. National Human Genome Research Institut. DNA Sequencing Costs: Data. Overview [cited 2018 Feb 20]. Available from: https://www.genome.gov/sequencingcostsdata/.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Философско-антропологические основания персонализированной медицины (междисциплинарный анализ): сб. науч. ст. / Под ред. Тищенко П.Д. ― М.: Издательство Московского гуманитарного университета; 2016.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Далантаева Н.С., Дедов И.И. Генетические и обменные особенности семейных изолированных аденом гипофиза // Ожирение и метаболизм. ― 2013. ― T.10. ― №2 ― C. 3–10. doi: 10.14341/2071-8713-4817.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Igreja S, Chahal HS, King P, et al. Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. Hum Mutat. 2010;31(8):950–960. doi: 10.1002/humu.21292.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Далантаева Н.С., Пигарова Е.А., Дзеранова Л.К., и др. Новые возможности в лечении и ведении акромегалии // Ожирение и метаболизм. ― 2012. ― T.9. ― №3 ― C. 29–32. doi: 10.14341/2071-8713-4970</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Wells SA, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. doi: 10.1089/thy.2014.0335.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915–1942. doi: 10.1210/jc.2014-1498.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med. 2010;363(24):2339–2350. doi: 10.1056/NEJMra0906948.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Zeggini E, Weedon MN, Lindgren CM, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007;316(5829):1336–1341. doi: 10.1126/science.1142364.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Потапов В.А. Поиск генетических маркеров, определяющих предрасположенность к сахарному диабету 2 типа: Автореф. дис. … канд. биол. наук. ― M; 2010. ― 25 C.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Kong Y, Sharma RB, Nwosu BU, Alonso LC. Islet biology, the CDKN2A/B locus and type 2 diabetes risk. Diabetologia. 2016;59(8):1579–1593. doi: 10.1007/s00125-016-3967-7.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>‘t Hart LM, Simonis-Bik AM, Nijpels G, et al. Combined risk allele score of eight type 2 diabetes genes is associated with reduced first-phase glucose-stimulated insulin secretion during hyperglycemic clamps. Diabetes. 2010;59(1):287–292. doi: 10.2337/db09-0736.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Hu C, Jia W. Linking MTNR1B variants to diabetes: the role of circadian rhythms. Diabetes. 2016;65(6):1490–1492. doi: 10.2337/dbi16-0012.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Lane JM, Chang AM, Bjonnes AC, et al. Impact of common diabetes risk variant in MTNR1B on sleep, circadian, and melatonin physiology. Diabetes. 2016;65(6):1741–1751. doi: 10.2337/db15-0999.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889–894. doi: 10.1126/science.1141634.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Feng X, Tucker KL, Parnell LD, et al. Insulin receptor substrate 1 (IRS1) variants confer risk of diabetes in the Boston Puerto Rican Health Study. Asia Pac J Clin Nutr. 2013;22(1):150–159. doi: 10.6133/apjcn.2013.22.1.09.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Ruggenenti P, Bettinaglio P, Pinares F, Remuzzi G. Angiotensin converting enzyme insertion/deletion polymorphism and renoprotection in diabetic and nondiabetic nephropathies. Clin J Am Soc Nephrol. 2008;3(5):1511–1525. doi: 10.2215/CJN.04140907.</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Алгоритмы специализированной медицинской помощи больным сахарным диабетом / Под редакцией И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. ― 8-й выпуск // Сахарный диабет. ― 2017. ― Т.20. ― №1S ― C. 1–121. doi: 10.14341/DM20171S8.</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Satoh M, Asayama K, Kikuya M, et al. Nocturnal blood pressure decline based on different time intervals and long-term cardiovascular risk: the Ohasama Study. Clin Exp Hypertens. 2018;40(1):1–7. doi: 10.1080/10641963.2016.1259324.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Legrain P, Aebersold R, Archakov A, et al. The human proteome project: current state and future direction. Mol Cell Proteomics. 2011;10(7):M111.009993. doi: 10.1074/mcp.M111.009993.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Duarte T, Spencer C. Personalized proteomics: the future of precision medicine. Proteomes. 2016;4(4):29. doi: 10.3390/proteomes4040029.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Archakov A, Aseev A, Bykov V, et al. Gene-centric view on the human proteome project: the example of the Russian roadmap for chromosome 18. Proteomics. 2011;11(10):1853–1856. doi: 10.1002/pmic.201000540.</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Dreesen J, Destouni A, Kourlaba G, et al. Evaluation of PCR-based preimplantation genetic diagnosis applied to monogenic diseases: a collaborative ESHRE PGD consortium study. Eur J Hum Genet. 2014;22(8):1012–1018. doi: 10.1038/ejhg.2013.277.</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Chen CK, Yu HT, Soong YK, Lee CL. New perspectives on preimplantation genetic diagnosis and preimplantation genetic screening. Taiwan J Obstet Gynecol. 2014;53(2):146–150. doi: 10.1016/j.tjog.2014.04.004.</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Shefi S, Raviv G, Rienstein S, et al. Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome. J Assist Reprod Genet. 2009;26(7):411–413. doi: 10.1007/s10815-009-9334-6.</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Baranov VS. Genome paths: a way to personalized and predictive medicine. Acta Naturae. 2009;1(3):70–80.</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Mutch DM, Clément K. Unraveling the genetics of human obesity. PLoS Genet. 2006;2(12):e188. doi: 10.1371/journal.pgen.0020188.</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Brother K, Rothstein M. Ethical, legal and social implications of incorporating personalized medicine into healthcare. Per Med. 2015;12(1):43–51. doi: 10.2217/pme.14.65.</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>congress.gov [Internet]. Congress of the USA. S.3822 ― Genomics and Personalized Medicine Act of 2006 [cited 2019 Jan 15]. Available from: https://www.congress.gov/bill/109th-congress/senate-bill/3822.</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>congress.gov [Internet]. Congress of the USA. H.R.6498 ― Genomics and Personalized Medicine Act of 2008 [cited 2019 Jan 15]. Available from: https://www.congress.gov/bill/110th-congress/house-bill/6498.</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>congress.gov [Internet]. Congress of the USA. H.R.5440 ― Genomics and Personalized Medicine Act of 2010 [cited 2019 Jan 15]. Available from: https://www.congress.gov/bill/111th-congress/house-bill/5440.</mixed-citation></ref></ref-list></back></article>
