<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<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">vestib</journal-id><journal-title-group><journal-title xml:lang="ru">Известия Национальной  академии наук Беларуси. Серия биологических наук</journal-title><trans-title-group xml:lang="en"><trans-title>Proceedings of the National Academy of Sciences of Belarus, Biological Series</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1029-8940</issn><issn pub-type="epub">2524-230X</issn><publisher><publisher-name>The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29235/1029-8940-2022-67-2-158-171</article-id><article-id custom-type="elpub" pub-id-type="custom">vestib-805</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>Молекулярно-генетические характеристики пациентов с сахарным диабетом</article-title><trans-title-group xml:lang="en"><trans-title>Molecular-genetic characteristics of patients with diabetes mellitus. Vestsi Natsyyanal’nai akademii navuk Belarusi</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>Лущик</surname><given-names>М. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Lushchyk</surname><given-names>M. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Лущик Максим Леонидович ‒ кандидат медицинских наук, доцент.</p><p>Ул. П. Бровки, 3/3, 220013, Минск</p></bio><bio xml:lang="en"><p>Maxim L. Lushchyk ‒ Ph. D. (Med.), Associate Professor.</p><p>3/3, P. Browka Str., 220013, Minsk</p></bio><email xlink:type="simple">maxim.lushchyk@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Амельянович</surname><given-names>М. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Ameliyanovich</surname><given-names>M. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Амельянович Максим Дмитриевич ‒ научный сотрудник.</p><p>Ул. Академическая, 27, 220072, Минск</p></bio><bio xml:lang="en"><p>Maxim D. Ameliyanovich – Researcher.</p><p>27, Akademicheskaya Str., 220072, Minsk</p></bio><email xlink:type="simple">M.Ameliyanovich@igc.by</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тузова</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Tuzava</surname><given-names>H. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Тузова Анна Александровна ‒ cтарший научный сотрудник.</p><p>Ул. П. Бровки, 3/3, 220013, Минск</p></bio><bio xml:lang="en"><p>Hanna A. Tuzava ‒ Senior Researcher.</p><p>3/3, P. Browka Str., 220013, Minsk</p></bio><email xlink:type="simple">tuzava@yahoo.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Моссэ</surname><given-names>И. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Mosse</surname><given-names>I. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Моссэ Ирма Борисовна – доктор биологических наук, профессор, главный научный сотрудник.</p><p>Ул. Академическая, 27, 220072, Минск</p></bio><bio xml:lang="en"><p>Irma B. Mosse ‒ D. Sс. (Biol.), Professor, Chief Researcher.</p><p>27, Akademicheskaya Str., 220072, Minsk</p></bio><email xlink:type="simple">I.Mosse@igc.by</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Данилова</surname><given-names>Л. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Danilova</surname><given-names>L. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Данилова Лариса Ивановна ‒ доктор медицинских наук, профессор, заведующий кафедрой.</p><p>Ул. П. Бровки, 3/3, 220013, Минск</p></bio><bio xml:lang="en"><p>Larisa I. Danilova ‒ D. Sс. (Med.), Professor, Head of the Department.3/3, P. Browka Str., 220013, Minsk</p></bio><email xlink:type="simple">Larisa.dan@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Белорусская медицинская академия последипломного образования</institution></aff><aff xml:lang="en"><institution>Belarusian Medical Academy of Postgraduate Education</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Институт генетики и цитологии, НАН Беларуси</institution></aff><aff xml:lang="en"><institution>Institute of Genetics and Cytology, National Academy of Sciences of Belarus</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>04</day><month>05</month><year>2022</year></pub-date><volume>67</volume><issue>2</issue><fpage>158</fpage><lpage>171</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Лущик М.Л., Амельянович М.Д., Тузова А.А., Моссэ И.Б., Данилова Л.И., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Лущик М.Л., Амельянович М.Д., Тузова А.А., Моссэ И.Б., Данилова Л.И.</copyright-holder><copyright-holder xml:lang="en">Lushchyk M.L., Ameliyanovich M.D., Tuzava H.A., Mosse I.B., Danilova L.I.</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://vestibio.belnauka.by/jour/article/view/805">https://vestibio.belnauka.by/jour/article/view/805</self-uri><abstract><p>В статье рассматриваются вопросы перспективности изучения полиморфных вариантов генов рецепторов, активируемых пероксисомным пролифератором (PPARs) трех типов (PPARα, PPARδ и PPARγ) при сахарном диабете (СД) с учетом их ключевой роли в регуляции энергетического гомеостаза, продукции провоспалительных цитокинов, контроле липидных характеристик и гликемии. Основной акцент сделан на применении методов скринингового тестирования пациентов на носительство однонуклеотидных полиморфизмов (ОНП) с целью совершенствования подходов к выделению групп риска формирования СД и ассоциированных заболеваний и последующей персонификации корригирующих мероприятий. Представлены клинико-лабораторная и молекулярно-генетические характеристики групп пациентов с СД 1-го и 2-го типа, здоровых добровольцев. Изучена распространенность ОНП в генах рецепторов, активируемых PPARs, у пациентов с СД по сравнению с таковой у лиц группы контроля. Среди оцененных ОНП наиболее четкую ассоциацию с СД показал rs135551 гена PPARA. Выявлены 4 варианта гаплотипов, достоверно ассоциированных с СД 1-го и 2-го типа. Обсуждается целесообразность дальнейшего уточнения клинической и генетической гетерогенности случаев диабета у пациентов групп СД1 и СД2. Оценены перспективы разработки превентивных технологий в диабетологии с использованием результатов долговременных эпидемиологических молекулярно-генетических скринингов.</p></abstract><trans-abstract xml:lang="en"><p>The article discusses the prospects for studying polymorphic variants of peroxisome proliferator-activated receptor genes (PPARs) of three types (PPARα, PPARδ, and PPARγ) in diabetes mellitus (DM), taking into account their key role in the regulation of energy homeostasis, production of pro-inflammatory cytokines, and lipid characteristics and glycemia control. The main emphasis is on the use of screening methods for testing patients for carriage of single nucleotide polymorphisms (SNPs) in order to improve approaches to identifying risk groups for the formation of DM and associated diseases, and subsequent personification of corrective measures. The clinical, laboratory and molecular genetic characteristics of groups of patients with type 1 and 2 diabetes, healthy volunteers are presented. The prevalence of SNPs in the genes of receptors activated by the peroxisome proliferator in patients with DM was studied in comparison with the control group. Among the evaluated SNPs of the rs135551 gene, PPARA showed the clearest association with the presence of DM. Four variants of haplotypes highly associated with DM1 and DM2 were identified. The expediency of further clarification of the clinical and genetic heterogeneity of cases of diabetes within the DM1 and DM2 groups is discussed. The prospects of this direction for the development of preventive technologies in diabetology, long-term epidemiological molecular genetic screenings are assessed.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>сахарный диабет</kwd><kwd>метаболические нарушения</kwd><kwd>молекулярно-генетические характеристики</kwd><kwd>однонуклеотидный полиморфизм</kwd><kwd>гаплотип</kwd><kwd>активируемые пероксисомным пролифератором рецепторы</kwd></kwd-group><kwd-group xml:lang="en"><kwd>diabetes mellitus</kwd><kwd>metabolic disorders</kwd><kwd>molecular genetics</kwd><kwd>single nucleotide polymorphism</kwd><kwd>haplotype</kwd><kwd>peroxisome proliferator-activated receptors</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено в рамках задания 6.1 «Разработать ДНК-технологию выявления генетического риска эндокринных заболеваний» научнотехнической программы Союзного государства «Разработка инновационных геногеографических и геномных технологий идентификации личности и индивидуальных особенностей человека на основе изучения генофондов регионов Союзного государства»</funding-statement><funding-statement xml:lang="en">The study was carried out as part of task 6.1 “Develop DNA technology for identifying the genetic risk of endocrine diseases” of the scientific and technical program of the Union State “Development of innovative genogeographic and genomic technologies for identifying a person and individual characteristics of a person based on studying the gene pools of the regions of the Union State”</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">Association of diabetes type and chronic diabetes complications with early exit from the labour force: register-based study of people with diabetes in Finland / O. Kurkela [et al.] // Diabetologia. ‒ 2021. ‒ Vol. 64, N 4. ‒ P. 795‒804. https://doi.org/10.1007/s00125-020-05363-6</mixed-citation><mixed-citation xml:lang="en">Kurkela O., Forma L., Ilanne-Parikka P., Nevalainen J., Rissanen P. Association of diabetes type and chronic diabetes complications with early exit from the labour force: register-based study of people with diabetes in Finland. Diabetologia, 2021, vol. 64, no. 4, pp. 795‒804. https://doi.org/10.1007/s00125-020-05363-6</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Частота абдоминального ожирения и ассоциированных с ним метаболических нарушений у детей 7‒13 лет / E. Г. Вайнилович [и др.] // Проблемы эндокринологии. ‒ 2011. ‒ Т. 57, № 5. ‒ С. 15‒23.</mixed-citation><mixed-citation xml:lang="en">Vainilovich E. G., Lushchik M. L., Sretenskaya Zh. L., Zapol’skii S. A., Danilova L. I. Frequency of abdominal obesity and associated metabolic disorders in children 7‒13 years old. Problemy endokrinologii [Endocrinology problems], 2011, vol. 57, no. 5, pp. 15‒23 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Genetic studies of body mass index yield new insights for obesity / A. E. Locke [et al.] // Nature. ‒ 2015. ‒ Vol. 518, N 7538. ‒ P. 197‒206. https://doi.org/10.1038/nature14177</mixed-citation><mixed-citation xml:lang="en">Locke A. E., Kahali B., Berndt S. I., Justice A. E., Pers T. H., Day F. R. [et al.]  Genetic studies of body mass index yield new insights for obesity. Nature, 2015, vol. 518, no. 7538, pp. 197‒206. https://doi.org/10.1038/nature14177</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">The trans-ancestral genomic architecture of glycemic traits / J. Chen [et al.] // Nat. Genet. ‒ 2021. ‒ Vol. 53, N 6. ‒ P. 840‒860. https://doi.org/10.1038/s41588-021-00852-9</mixed-citation><mixed-citation xml:lang="en">Chen J., Spracklen C. N., Marenne G., Varshney A., Corbin L. J., Luan J. [et al.] The trans-ancestral genomic architecture of glycemic traits. Nature Genetics, 2021, vol. 53, no. 6, pp. 840‒860. https://doi.org/10.1038/s41588-021-00852-9</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Goodarzi, M. O. Genetics insights in the relationship between type 2 diabetes and coronary heart disease / M. O. Goodarzi, J. I. Rotter // Circ. Res. ‒ 2020. ‒ Vol. 126, N 11. ‒ P. 1526–1548. https://doi.org/10.1161</mixed-citation><mixed-citation xml:lang="en">Goodarzi M. O., Rotter J. I. Genetics insights in the relationship between type 2 diabetes and coronary heart disease.  Circulation Research, 2020, vol. 126, no. 11, pp. 1526–1548. https://doi.org/10.1161</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria / F. Day [et al.] // PLOS Genetics. ‒ 2018. ‒ Vol. 14, N 12. ‒ P. 1‒20. https://doi.org/10.1371/journal.pgen.1007813</mixed-citation><mixed-citation xml:lang="en">Day F., Karaderi T., Jones M. R., Meun C., Chunyan He, Drong A. [et al.]. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLOS Genetics, 2018, vol. 14, no. 12, pp. 1‒20.  https://doi.org/10.1371/journal.pgen.1007813</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Groop, L. New approaches beyond genetics: towards precision medicine in diabetes / L. Groop // Diabetologia. ‒ 2016. ‒ Vol. 59, N 12. ‒ P. 2495‒2496. https://doi.org/10.1007/s00125-016-4014-4</mixed-citation><mixed-citation xml:lang="en">Groop L. New approaches beyond genetics: towards precision medicine in diabetes. Diabetologia, 2016, vol. 59, no. 12, pp. 2495‒2496.  https://doi.org/10.1007/s00125-016-4014-4</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">American Diabetes Association. Standards of medical care in diabetes-2019 abridged for primary care providers // Clin. Diabetes. ‒ 2019. ‒ Vol. 37, N 1. ‒ P. 11‒34. https://doi.org/10.2337/cd18-0105</mixed-citation><mixed-citation xml:lang="en">American Diabetes Association. Standards of medical care in diabetes-2019 abridged for primary care providers. Clinical Diabetes, 2019, vol. 37, no. 1, pp. 11‒34.  https://doi.org/10.2337/cd18-0105</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Pollanen, P. M. Dynamics of islet autoantibodies during prospective follow-up from birth to age 15 years / P. M. Pollanen, S. J. Ryhanen, J. Toppari // J. Clin. Endocrinol. Metab. ‒ 2020. ‒ Vol. 105, N 12. ‒ P. e4638–e4651. https://doi.org/10.1210/clinem/dgaa624</mixed-citation><mixed-citation xml:lang="en">Pollanen P. M., Ryhanen S. J., Toppari J. Dynamics of islet autoantibodies during prospective follow-up from birth to age 15 years. Journal of Clinical Endocrinology &amp; Metabolism, 2020, vol. 105, no. 12, pp. e4638–e4651. https://doi.org/10.1210/clinem/dgaa624</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">American Diabetes Association Professional Practice Committee. Classification and diagnosis of diabetes: standarts of medical care of diabetes-2022. Diabetes care / B. Draznin [et al.]. ‒ 2022. ‒ Vol. 45, suppl. 1. ‒ P. S17‒S38. https://doi.org/10.2337/dc22-S002</mixed-citation><mixed-citation xml:lang="en">Draznin B., Aroda V. R., Bakris G., Benson G., Brown F. M., Freeman R. [et al.]. American Diabetes Association Professional Practice Committee. Classification and diagnosis of diabetes: standarts of medical care of diabetes-2022. Diabetes Care, 2022, vol. 45, suppl. 1, pp. S17‒S38. https://doi.org/10.2337/dc22-S002</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Alberti, K. G. Metabolic syndrome ‒ a new world-wide definition. A Consensus Statement from the International Diabetes Federation / K. G. Alberti, P. Zimmet, J. Shaw // Diabet. Medicine. ‒ 2006. ‒ Vol. 23, N 5. ‒ P. 469–480. https://doi.org/10.1111/j.1464-5491</mixed-citation><mixed-citation xml:lang="en">Alberti K. G., Zimmet P., Shaw J.  Metabolic syndrome ‒ a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabetic Medicine, 2006, vol. 23, no. 5, pp. 469–480. https://doi.org/10.1111/j.1464-5491.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Khosla, T. Indices of obesity derived from body weight and height / T. Khosla, C. R. Lowe // J. Epid. Commun. Health. ‒ 1967. ‒ Vol. 21, N 3. ‒ P. 122‒128. https://doi.org/10.1136/jech.21.3.122</mixed-citation><mixed-citation xml:lang="en">Khosla T., Lowe C. R. Indices of obesity derived from body weight and height. Journal of Epidemiology and Community Health, 1967, vol. 21, no. 3, pp. 122‒128. https://doi.org/10.1136/jech.21.3.122</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Risk assessment of type 2 diabetes in northern China based on the logistic regression model / C. Li [et al.] // Technol. Health Care. ‒ 2021. ‒ Vol. 29, N S1. ‒ P. S351–S358. https://doi.org/10.3233/THC-218033</mixed-citation><mixed-citation xml:lang="en">Li C., Liu M., An Y., Tian Y., Di Guan, Wu H., Pei Z. Risk assessment of type 2 diabetes in northern China based on the logistic regression model. Technology and Health Care, 2021, vol. 29, no. S1, pp. S351–S358. https://doi.org/10.3233/THC-218033</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Реброва, O. Ю. Статистический анализ медицинских данных. Применение пакета прикладных программ STATISTICA / O. Ю. Реброва. ‒ M. : Медиасфера, 2002. ‒ 305 с.</mixed-citation><mixed-citation xml:lang="en">Rebrova O. Yu. Statistical analysis of medical data. Using the STATISTICA Application Package. Moscow, Mediasfera Publ., 2002. 305 p. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Consensus report: definition and interpretation of remission in type 2 diabetes / M. C. Riddle [et al.] // Diabetologia. ‒ 2021. ‒ Vol. 64, N 11. ‒ P. 2359‒2366. https://doi.org/10.1007/s00125-021-05542-z</mixed-citation><mixed-citation xml:lang="en">Riddle M. C., Cefalu W. T., Evans P. H., Gerstein H. C., Nauck M. A., Oh W. K. [et al.].  Consensus report: definition and interpretation of remission in type 2 diabetes. Diabetologia, 2021, vol. 64, no. 11, pp. 2359‒2366. https://doi.org/10.1007/s00125-021-05542-z</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">PPAR agonists and metabolic syndrome: an established role? / M. Botta [et al.] // Int. J. Mol. Sci. ‒ 2018. ‒ Vol. 19, N 4. ‒ Art. 1197. https://doi.org/10.3390/ijms19041197</mixed-citation><mixed-citation xml:lang="en">Botta M., Audano M., Sahebkar A., Sirtori C. R., Mitro N., Ruscica M. PPAR agonists and metabolic syndrome: an established role? International Journal of Molecular Sciences, 2018, vol. 19, no. 4, art. 1197. https://doi.org/10.3390/ijms19041197</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Mirza, A. Z. Role of PPAR receptor in different diseases and their ligands: physiological importance and clinical implications / A. Z. Mirza, I. I. Althagafi, H. Shamshad // Eur. J. Med. Chem. ‒ 2019. ‒ Vol. 166. ‒ P. 502‒513 https://doi.org/10.1016/j.ejmech.2019.01.067</mixed-citation><mixed-citation xml:lang="en">Mirza A. Z., Althagafi I. I., Shamshad H. Role of PPAR receptor in different diseases and their ligands: physiological importance and clinical implications. European Journal of Medicinal Chemistry, 2019, vol. 166, pp. 502‒513. https://doi.org/10.1016/j.ejmech.2019.01.067</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Guo, Z. Current progress in pharmacogenomics of type 2 diabetes: a systemic overview / Z. Guo, R. Priefer // Diabetes Metab. Syndr. ‒ 2021. ‒ Vol. 15, N 5. ‒ P. 20, 102239. https://doi.org/10.1016/j.dsx.2021.102239</mixed-citation><mixed-citation xml:lang="en">Guo Z., Priefer R. Current progress in pharmacogenomics of type 2 diabetes: a systemic overview. Diabetes and Metabolic Syndrome, 2021, vol. 15, no. 5, p. 20, 102239. https://doi.org/10.1016/j.dsx.2021.102239</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Exploration and development of PPAR modulators in health and disease: an update of clinical evidence / H. S. Cheng [et al.] // Int. J. Mol. Sci. ‒ 2019. ‒ Vol. 20, N 20. ‒ Art. 5055. https://doi.org/10.3390/ijms20205055</mixed-citation><mixed-citation xml:lang="en">Cheng H. S., Tan W. R., Low Z. S., Marvalim Ch., Hao Leе J. Y., Tan N. S. Exploration and development of PPAR modulators in health and disease: an update of clinical evidence. International Journal of Molecular Sciences, 2019, vol. 20, no. 20, art. 5055. https://doi.org/10.3390/ijms20205055</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ) : a review / L. Wang [et al.] // Biochem. Pharmacol. ‒ 2014. ‒ Vol. 92, N 1. ‒ P. 73‒89. https://doi.org/10.1016/j.bcp.2014.07.018</mixed-citation><mixed-citation xml:lang="en">Wang L., Waltenberger B., Pferschy-Wenzig E. M., Blunder M., Liu X., Malainer C. [et al.]. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochemical Pharmacology, 2014, vol. 92, no. 1, pp. 73‒89. https://doi.org/10.1016/j.bcp.2014.07.018</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part II: PPAR-β/δ and PPAR-γ / L. Han [et al.] // Future Cardiol. ‒ 2017. ‒ Vol. 13, N 3. ‒ P. 279‒296. https://doi.org/10.2217/fca-2017-0019</mixed-citation><mixed-citation xml:lang="en">Han L., Shen W. J., Bittner S., Kraemer F. B., Azhar S. PPARs: regulators of metabolism and as therapeutic targets in cardiovascular disease. Part II: PPAR-β/δ and PPAR-γ. Future Cardiology, 2017, vol. 13, no. 3, pp. 279‒296. https://doi.org/10.2217/fca-2017-0019</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Distinct but complementary contributions of PPAR isotypes to energy homeostasis / V. Dubois [et al.] // J. Clin. Invest. ‒ 2017. ‒ Vol. 127, N 4. ‒ P. 1202‒1214. https://doi.org/10.1172/JCI88894</mixed-citation><mixed-citation xml:lang="en">Dubois V., Eeckhoute J., Lefebvre P., Staels B. Distinct but complementary contributions of PPAR isotypes to energy homeostasis. Journal of Clinical Investigation, 2017, vol. 127, no. 4, pp. 1202‒1214. https://doi.org/10.1172/JCI88894</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Muzio, G. Peroxisome proliferator-activated receptors (PPARs) and oxidative stress in physiological conditions and in cancer / G. Muzio, G. Barrera, S. Pizzimenti // Antioxidants (Basel). ‒ 2021. ‒ Vol. 10, N 11. ‒ Art. 1734. https://doi.org/10.3390/antiox10111734</mixed-citation><mixed-citation xml:lang="en">Muzio G., Barrera G., Pizzimenti S. Peroxisome proliferator-activated receptors (PPARs) and oxidative stress in physiological conditions and in cancer. Antioxidants (Basel), 2021, vol. 10, no. 11, art. 1734. https://doi.org/10.3390/antiox10111734</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study / C. Thamer [et al.] // J. Clin. Endocrinol. Metab. ‒ 2008. ‒ Vol. 93, N 4. ‒ P. 1497‒1500. https://doi.org/10.1210/jc.2007-1209</mixed-citation><mixed-citation xml:lang="en">Thamer C., Machann J., Stefan N., Schäfer S. A., Machicao F., Staiger H. [et al.]. Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study. Journal of Clinical Endocrinology and Metabolism, 2008, vol. 93, no. 4, pp. 1497‒500. https://doi.org/10.1210/jc.2007-1209</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">West of Scotland Coronary Prevention Study. Peroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men / J. Skogsberg [et al.] // J. Int. Med. ‒ 2003. ‒ Vol. 254, N 6. ‒ P. 597‒604. https://doi.org/10.1111/j.1365-2796.2003.01236.x</mixed-citation><mixed-citation xml:lang="en">Skogsberg J., McMahon A. D., Karpe F., Hamsten A., Packard C. J., Ehrenborg E. West of Scotland Coronary Prevention Study. Peroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men. Journal of Internal Medicine, 2003, vol. 254, no. 6, pp. 597‒604. https://doi.org/10.1111/j.1365-2796.2003.01236.x</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Association of peroxisome proliferator-activated receptor α/δ/γ with obesity, and gene-gene interaction, in the Chinese Han population / W. Luo [et al.] // J. Epidemiol. ‒ 2013. ‒ Vol. 23, N 3. ‒ P. 187–194. https://doi.org/10.2188/jea.je20120110</mixed-citation><mixed-citation xml:lang="en">Luo W., Guo Z., Wu M., Hao C., Hu X., Zhou Z., Zhou Z., Yao X., Zhang L., Liu J. Association of peroxisome proliferatoractivated receptor α/δ/γ with obesity, and gene-gene interaction, in the Chinese Han population. Journal of Epidemiology, 2013, vol. 23, no. 3, pp. 187–194. https://doi.org/10.2188/jea.je20120110</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Association and interaction of PPARα, δ, and γ gene polymorphisms with low-density lipoprotein-cholesterol in a Chinese Han population / W. Fan [et al.] // Gen. Test Mol. Biomarkers. ‒ 2015. ‒ Vol. 19, N 7. ‒ P. 379‒386. https://doi.org/10.1089/gtmb.2015.0002</mixed-citation><mixed-citation xml:lang="en">Fan W., Shen C., Wu M., Zhou Z. Y., Guo Z. R. Association and interaction of PPARα, δ, and γ gene polymorphisms with low-density lipoprotein-cholesterol in a Chinese Han population. Genetic Testing and Molecular Biomarkers, 2015, vol. 19, no. 7, pp. 379‒386. https://doi.org/10.1089/gtmb.2015.0002</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">The role of peroxisome proliferator-activated receptors α polymorphisms in Graves’ disease and orbitopathy / J. P. Przemyslaw [et al.] // Endocrine Abstracts. ‒ 2014. ‒ Vol. 35. ‒ Art. P1028. https://doi.org/10.1530/endoabs.35.P1028</mixed-citation><mixed-citation xml:lang="en">Janusz P., Pawlak-Adamska E., Bolanowski M., Daroszewski J. The role of peroxisome proliferator-activated receptors α polymorphisms in Graves’ disease and orbitopathy. Endocrine Abstracts, 2014, art. P1028. https://doi.org/10.1530/endoabs.35.P1028</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Interaction between peroxisome proliferator-activated receptor gamma polymorphism and obesity on type 2 diabetes in a Chinese Han population / X. Lv [et al.] // Diabetol. Metab. Syndr. ‒ 2017. ‒ Vol. 19. ‒ Art. 7. https://doi.org/10.1186/s13098017-0205-5</mixed-citation><mixed-citation xml:lang="en">Lv X., Zhang L., Sun J., Cai Z., Gu Q., Zhang R., Shan A. Interaction between peroxisome proliferator-activated receptor gamma polymorphism and obesity on type 2 diabetes in a Chinese Han population. Diabetology and Metabolic Syndrome, 2017, vol. 19, art. 7. https://doi.org/10.1186/s13098-017-0205-5</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Associations of type 2 diabetes with common variants in PPARD and the modifying effect of vitamin D among middle-aged and elderly Chinese / L. Lu [et al.] // PLoS ONE. ‒ 2012. ‒ Vol. 7, N 4. ‒ P. e34895. https://doi.org/10.1371/journal.pone.0034895</mixed-citation><mixed-citation xml:lang="en">Lu L., Wu Y., Qi Q., Liu C., Gan W., Zhu J. [et al.] Associations of type 2 diabetes with common variants in PPARD and the modifying effect of vitamin D among middle-aged and elderly Chinese. PLoS ONE, 2012, vol. 7, no. 4, p. e34895. https://doi.org/10.1371/journal.pone.0034895</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Du, F. Correlation between PPARGC1A gene rs8192678 G&gt;A polymorphism and susceptibility to type-2 diabetes / F. Du, K.-J. Yang, L.-S. Piao // Open Life Sci. ‒ 2019. ‒ Vol. 14, N 1. ‒ P. 43‒52. https://doi.org/10.1515/biol-2019-0006</mixed-citation><mixed-citation xml:lang="en">Du F., Yang K.-J., Piao L.-S. Correlation between PPARGC1A gene rs8192678 G&gt;A polymorphism and susceptibility to type-2 diabetes. Open Life Sciences, 2019, vol. 14, no. 1, pp. 43‒52. https://doi.org/10.1515/biol-2019-0006</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Meta-analysis demonstrates Gly482Ser variant of PPARGC1A is associated with components of metabolic syndrome within Asian populations / P. Bhatta [et al.] // Genomics. ‒ 2020. ‒ Vol. 112, N 2. ‒ P. 1795‒1803. https://doi.org/10.1016/j.ygeno.2019.10.011</mixed-citation><mixed-citation xml:lang="en">Bhatta P., Bermano G., Williams H. C., Knott R. M. Meta-analysis demonstrates Gly482Ser variant of PPARGC1A is associated with components of metabolic syndrome within Asian populations. Genomics, 2020, vol. 112, no. 2, pp. 1795‒1803. https://doi.org/10.1016/j.ygeno.2019.10.011</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Ahlqvist, Е. Subtypes of type 2 diabetes determined from clinical parameters / Е. Ahlqvist, R. B. Prasad // Diabetes. ‒ 2020. ‒ Vol. 69, N 10. ‒ P. 2086–2093. https://doi.org/10.2337/dbi20-0001</mixed-citation><mixed-citation xml:lang="en">Ahlqvist Е., Prasad R. B. Subtypes of type 2 diabetes determined from clinical parameters. Diabetes, 2020, vol. 69, no. 10, pp. 2086–2093. https://doi.org/10.2337/dbi20-0001</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">The many faces of diabetes: a disease with increasing heterogeneity / T. Tuomi [et al.] // Lancet. ‒ 2014. ‒ Vol. 383, N 9922. ‒ P. 1084–1094. https://doi.org/10.1016/S0140-6736(13)62219-9</mixed-citation><mixed-citation xml:lang="en">Tuomi T., Santoro N., Caprio S., Cai M., Weng J., Groop L. The many faces of diabetes: a disease with increasing heterogeneity. Lancet, 2014, vol. 383, no. 9922, pp. 1084–1094. https://doi.org/10.1016/S0140-6736(13)62219-9</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Pearson, E. R. Type 2 diabetes: a multifaceted disease / E. R. Pearson // Diabetologia. ‒ 2019. ‒ Vol. 62. ‒ P. 1107–1112. https://doi.org/10.1007/s00125-019-4909-y</mixed-citation><mixed-citation xml:lang="en">Pearson E. R. Type 2 diabetes: a multifaceted disease. Diabetologia, 2019, vol. 62, pp. 1107–1112. https://doi.org/10.1007/s00125-019-4909-y</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment / R. D. Leslie [et al.] // Diabetologia. ‒ 2016. ‒ Vol. 59, N 1. ‒ P. 13‒20. https://doi.org/10.1007/s00125-015-3789-z</mixed-citation><mixed-citation xml:lang="en">Leslie R. D., Palmer J., Schloot N. C., Lernmark A. Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment. Diabetologia, 2016, vol. 59, no. 1, pp. 13‒20. https://doi.org/10.1007/s00125-015-3789-z</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks? / S. J. Cleland [et al.] // Diabetologia. ‒ 2013. ‒ Vol. 56. ‒ P. 1462–1470. https://doi.org/10.1007/s00125-013-2904-2</mixed-citation><mixed-citation xml:lang="en">Cleland S. J., Fisher B. M., Colhoun H. M., Sattar N., Petrie J. R. Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks? Diabetologia, 2013, vol. 56, pp. 1462–1470.  https://doi.org/10.1007/s00125-013-2904-2</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Two decades since the fetal insulin hypothesis: what have we learned from genetics? / A. E. Hughes [et al.] // Diabetologia. ‒ 2021. ‒ Vol. 64, N 3. ‒ P. 717‒726. https://doi.org/10.1007/s00125-021-05386-7</mixed-citation><mixed-citation xml:lang="en">Hughes A. E., Hattersley T. A., Flanagan S. E., Freathy R. M. Two decades since the fetal insulin hypothesis: what have we learned from genetics? Diabetologia, 2021, vol. 64, no. 3, pp. 717‒726. https://doi.org/10.1007/s00125-021-05386-7</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Wolosowicz, M. The causes of insulin resistance in type 1 diabetes mellitus: is there a place for quaternary prevention? / M. Wolosowicz, B. Lukaszuk, A. Chabowski // Int. J. Environ. Res. Publ. Health. ‒ 2020. ‒ Vol. 17, N 22. ‒ Art. 8651. https://doi.org/10.3390/ijerph17228651</mixed-citation><mixed-citation xml:lang="en">Wolosowicz M., Lukaszuk B., Chabowski A. The causes of insulin resistance in type 1 Diabetes Mellitus: is there a place for quaternary prevention? International Journal of Environmental Research and Public Health, 2020, vol. 17, no. 22, art. 8651. https://doi.org/10.3390/ijerph17228651</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Franks, P. W. Gene-lifestyle interplay in type 2 diabetes / P. W. Franks, J. Merino // Curr. Opin. Gen. Dev. ‒ 2018. ‒ Vol. 50, N 6. ‒ P. 35–40. https://doi.org/10.1016/j.gde.2018.02.001</mixed-citation><mixed-citation xml:lang="en">Franks P. W., Merino J. Gene-lifestyle interplay in type 2 diabetes. Current Opinion in Genetics and Development, 2018, vol. 50, no. 6, pp. 35–40. https://doi.org/10.1016/j.gde.2018.02.001</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Obesity subtypes, related biomarkers &amp; heterogeneity / L. P. Mayoral [et al.] // Indian J. Med. Res. ‒ 2020. ‒ Vol. 151, N 1. ‒ P. 11‒21. https://doi.org/10.4103/ijmr.IJMR_1768_17</mixed-citation><mixed-citation xml:lang="en">Mayoral L. P., Andrade G. M., Mayoral E. P., Huerta T. H., Canseco S. P., Rodal Canales F. J. [et al.]. Obesity subtypes, related biomarkers &amp; heterogeneity. Indian Journal of Medical Research, 2020, vol. 151, no. 1, pp. 11‒21. https://doi.org/10.4103/ijmr.IJMR_1768_17</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>
