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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">endofocus</journal-id><journal-title-group><journal-title xml:lang="ru">FOCUS Эндокринология</journal-title><trans-title-group xml:lang="en"><trans-title>FOCUS. Endocrinology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2713-0177</issn><issn pub-type="epub">2713-0185</issn><publisher><publisher-name>ООО "Издательство "Перо"</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.62751/2713-0177-2026-7-1-01</article-id><article-id custom-type="elpub" pub-id-type="custom">endofocus-187</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 ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL RESEARCH</subject></subj-group></article-categories><title-group><article-title>Генетические маркеры риска развития сахарного диабета 1 типа в HLA-комплексе у детей Поволжья</article-title><trans-title-group xml:lang="en"><trans-title>Genetic risk markers of type 1 diabetes within the HLA complex in children of the Volga region</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3293-4636</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Корнева</surname><given-names>К. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Korneva</surname><given-names>K. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ксения Георгиевна Корнева, к.м.н., доцент</p><p>кафедра эндокринологии и внутренних болезней</p><p>603000; пл. Минина и Пожарского д. 10/1; Нижний Новгород</p></bio><bio xml:lang="en"><p>Kseniya G. Korneva, Cand. Sci. (Med.), Associate Professor</p><p>603000; 10/1 Minin and Pozharsky square; Nizhny Novgorod</p></bio><email xlink:type="simple">ksenkor@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/0000-0001-9621-5732</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Безлепкина</surname><given-names>О. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Bezlepkina</surname><given-names>O. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ольга Борисовна Безлепкина, д.м.н., профессор, директор Института</p><p>Институт детской эндокринологии</p><p>Москва</p></bio><bio xml:lang="en"><p>Olga B. Bezlepkina,  Dr. Sci. (Med.), Professor, director of the Institute</p><p>Institute of pediatric endocrinology</p><p>Moscow</p></bio><email xlink:type="simple">olga.bezlepkina@endocrincentr.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/0000-0001-8610-5054</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шаронов</surname><given-names>Г. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Sharonov</surname><given-names>G. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Георгий Владимирович Шаронов, к.ф.-м.н., старший научный сотрудник</p><p>Нижний Новгород; Москва</p></bio><bio xml:lang="en"><p>George V. Sharonov, Cand. Sci. (Phys.-Math.)</p><p>Nizhny Novgorod; Moscow</p></bio><email xlink:type="simple">sharonov@gmail.com</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3752-5612</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шабалкина</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Shabalkina</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Александра Валерьевна Шабалкина, спирант</p><p>Москва; Московская область; Долгопрудный</p></bio><bio xml:lang="en"><p>Alexandra V. Shabalkina,  postgraduate student</p><p>Moscow; Moscow Region; Dolgoprudny,</p></bio><email xlink:type="simple">av.shabalkina@gmail.com</email><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4467-5010</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сальникова</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Salnikova</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мария Алексеевна Сальникова, младший научный сотрудник</p><p>Москва</p></bio><bio xml:lang="en"><p>Mariia A. Salnikova, junior researcher</p><p>Moscow</p></bio><email xlink:type="simple">msalniku@yandex.ru</email><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3954-9108</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шагина</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Shagina</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ирина Александровна Шагина, к. б. н., научный сотрудник</p><p>Москва</p></bio><bio xml:lang="en"><p>Irina A. Shagina, Cand. Sci. (Biol.)</p><p>Moscow</p></bio><email xlink:type="simple">irishashagina@gmail.com</email><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6436-3386</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чичеватов</surname><given-names>Д. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Chichevatov</surname><given-names>D. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Дмитрий Андреевич Чичеватов, д. м. н., профессор</p><p>Пенза</p></bio><bio xml:lang="en"><p>Dmitry A. Chichevatov, Dr. Sci. (Med.), professor</p><p>Penza</p></bio><email xlink:type="simple">chichevatov69@mail.ru</email><xref ref-type="aff" rid="aff-6"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2645-2729</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Стронгин</surname><given-names>Л. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Strongin</surname><given-names>L. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Леонид Григорьевич Стронгин, д. м. н., профессор</p><p>Нижний Новгород</p></bio><bio xml:lang="en"><p>Leonid G. Strongin, Dr. Sci. (Med.)</p><p>Nizhny Novgorod</p></bio><email xlink:type="simple">malstrong@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5769-0378</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Загайнов</surname><given-names>В. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Zagainov</surname><given-names>V. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Владимир Евгеньевич Загайнов, д. м. н.</p><p>Нижний Новгород</p></bio><bio xml:lang="en"><p>Vladimir E. Zagainov, Dr. zSci. (Med.)</p><p>Nizhny Novgorod</p></bio><email xlink:type="simple">zagainov@mail.com</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Приволжский исследовательский медицинский университет</institution></aff><aff xml:lang="en"><institution>Privolzhsky Research Medical University</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Национальный медицинский исследовательский центр эндокринологии имени академика И.И. Дедова</institution></aff><aff xml:lang="en"><institution>I.I. Dedov National Medical Research Center of Endocrinology</institution></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Приволжский исследовательский медицинский университет; Российский национальный исследовательский медицинский университет имени Н.И. Пирогова (Пироговский университет); Институт биоорганической химии имени академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук</institution></aff><aff xml:lang="en"><institution>Privolzhsky Research Medical University; Pirogov Russian National Research Medical University; Shemyakin – Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Science</institution></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>Российский национальный исследовательский медицинский университет имени Н.И. Пирогова (Пироговский университет); Институт биоорганической химии имени академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук; Московский физико-технический институт (национальный исследовательский университет)</institution></aff><aff xml:lang="en"><institution>Pirogov Russian National Research Medical University; Shemyakin – Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Science; Moscow Institute of Physics and Technology, Moscow Region</institution></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru"><institution>Российский национальный исследовательский медицинский университет имени Н.И. Пирогова (Пироговский университет); Институт биоорганической химии имени академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук</institution></aff><aff xml:lang="en"><institution>Pirogov Russian National Research Medical University; Shemyakin – Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Science</institution></aff></aff-alternatives><aff-alternatives id="aff-6"><aff xml:lang="ru"><institution>Пензенский государственный университет</institution></aff><aff xml:lang="en"><institution>Penza state University</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>03</day><month>05</month><year>2026</year></pub-date><volume>7</volume><issue>1</issue><fpage>5</fpage><lpage>13</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Корнева К.Г., Безлепкина О.Б., Шаронов Г.В., Шабалкина А.В., Сальникова М.А., Шагина И.А., Чичеватов Д.А., Стронгин Л.Г., Загайнов В.Е., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Корнева К.Г., Безлепкина О.Б., Шаронов Г.В., Шабалкина А.В., Сальникова М.А., Шагина И.А., Чичеватов Д.А., Стронгин Л.Г., Загайнов В.Е.</copyright-holder><copyright-holder xml:lang="en">Korneva K.G., Bezlepkina O.B., Sharonov G.V., Shabalkina A.V., Salnikova M.A., Shagina I.A., Chichevatov D.A., Strongin L.G., Zagainov V.E.</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://endofocus.elpub.ru/jour/article/view/187">https://endofocus.elpub.ru/jour/article/view/187</self-uri><abstract><sec><title>   Актуальность</title><p>   Актуальность. Сахарный диабет 1 типа (СД1) характеризуется выраженной генетической гетерогенностью, при этом ключевую роль в формировании риска играют гены комплекса HLA. Распределение и вклад HLA-аллелей и гаплотипов существенно варьируют между популяциями, что обусловливает необходимость изучения популяционно-специфических особенностей генетической предрасположенности в разных когортах.</p></sec><sec><title>   Цель исследования</title><p>   Цель исследования. Изучить спектр и частоту встречаемости HLA-генов и гаплотипов, ассоциированных с риском развития СД1 в регионах Поволжья.</p></sec><sec><title>   Материал и методы</title><p>   Материал и методы. Проведено многоцентровое сравнительное исследование с участием 507 детей, включая 310 пациентов с впервые выявленным СД1 и 197 их здоровых сибсов из трех регионов Поволжья. HLA-типирование (локусы HLA-A, -B, -C, -DR, -DQ, -DP) выполнялось методом аллель-специфической полимеразной цепной реакции с последующим секвенированием.</p></sec><sec><title>   Результаты</title><p>   Результаты. У пациентов с СД1 выявлены выраженные различия в распределении гаплотипов HLA II класса по сравнению со здоровыми сибсами. Гаплотипы DR3–DQ2 и DR4–DQ8 достоверно ассоциировались с повышенным риском заболевания, тогда как DRB1*15:01–DQA1*01:02–DQB1*06:02 и DRB1*07:01–DQA1*02:01–DQB1*03:03 проявляли выраженный протективный эффект. Для локуса DPB1 наблюдались разнонаправленные ассоциации: аллель DPB1*01:01 был ассоциирован с повышенным риском СД1, тогда как DPB1*04:02 со снижением риска. Анализ взаимодействий показал преимущественно аддитивный характер влияния DPB1 и гаплотипов DR–DQ без признаков эпистатических эффектов. Среди локусов HLA I класса аллели B*08:01 и B*39:01 ассоциировались с повышенным риском развития СД1, тогда как B*57:01 демонстрировала протективное действие. Межклассовые взаимодействия HLA I и II классов в целом носили суммарный характер, а выявленные ассоциации частично объяснялись неравновесным сцеплением в пределах HLA-региона.</p></sec><sec><title>   Заключение</title><p>   Заключение. Подтверждена ведущая роль гаплотипов HLA II класса (DR3–DQ2 и DR4–DQ8) в формировании генетической предрасположенности к СД1. Гаплотипы DRB1*15:01–DQA101:02–DQB1*06:02 и DRB1*07:01–DQA1*02:01–DQB1*03:03 ассоциированы со сниженным риском заболевания. Локусы HLA I класса и DPB1 вносят дополнительный преимущественно аддитивный вклад в риск СД1, при этом DPB1*01:01 связан с повышенным риском, а DPB1*04:02 и B*57:01 – с протективным эффектом.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>   Background</title><p>   Background. Type 1 diabetes mellitus (T1DM) is characterized by pronounced genetic heterogeneity, with genes of the HLA complex playing a key role in disease susceptibility. The distribution and contribution of HLA alleles and haplotypes vary substantially between populations, highlighting the need to study population-specific features of genetic predisposition in different cohorts.</p></sec><sec><title>   The aim</title><p>   The aim: to investigate the spectrum and frequency of HLA genes and haplotypes associated with the risk of T1DM in the Volga region.</p></sec><sec><title>   Material and methods</title><p>   Material and methods. A multicenter comparative study included 507 children: 310 patients with newly diagnosed T1DM and 197 healthy siblings from three regions of the Volga area. HLA typing of loci HLA-A, -B, -C, -DR, -DQ, and -DP was performed using allele-specific PCR followed by sequencing.</p></sec><sec><title>   Results</title><p>   Results. Patients with T1DM demonstrated significant differences in the distribution of HLA class II haplotypes compared with healthy siblings. The DR3–DQ2 and DR4–DQ8 haplotypes were significantly associated with increased disease risk, whereas DRB1*15:01–DQA1*01:02–DQB1*06:02 and DRB1*07:01–DQA1*02:01–DQB1*03:03 showed a strong protective effect. For the DPB1 locus, opposite associations were observed: DPB1*01:01 was associated with increased T1DM risk, while DPB1*04:02 was associated with reduced risk. Interaction analysis indicated a predominantly additive effect of DPB1 and DR–DQ haplotypes, without evidence of epistatic interactions. Among HLA class I loci, B*08:01 and B*39:01 were associated with increased T1DM risk, whereas B*57:01 demonstrated a protective effect. Interactions between HLA class I and class II loci were generally additive, and some associations were partially explained by linkage disequilibrium within the HLAregion.</p></sec><sec><title>   Conclusion</title><p>   Conclusion. The leading role of HLA class II haplotypes (DR3–DQ2 and DR4–DQ8) in genetic susceptibility to type 1 diabetes was confirmed. The haplotypes DRB1*15:01–DQA1*01:02–DQB1*06:02 and DRB1*07:01–DQA1*02:01–DQB1*03:03 were associated with reduced disease risk. HLA class I loci and DPB1 provide an additional, predominantly additive contribution to T1DM risk, with DPB1*01:01 conferring increased risk and DPB1*04:02 and B*57:01 showing protective effects.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>сахарный диабет 1 типа</kwd><kwd>сибсы</kwd><kwd>HLА-гаплотип</kwd><kwd>генетическая предрасположенность</kwd></kwd-group><kwd-group xml:lang="en"><kwd>type 1 diabetes mellitus</kwd><kwd>siblings</kwd><kwd>HLA haplotypes</kwd><kwd>genetic susceptibility</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Отсутствует</funding-statement><funding-statement xml:lang="en">None</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">Akil AA, Yassin E, Al-Maraghi A, Aliyev E, Al-Malki K, Fakhro KA. Diagnosis and treatment of type 1 diabetes at the dawn of the personalized medicine era. 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