aterosklerozАтеросклерозAteroscleroz2078-256X2949-3633НИИТПМ-филиал ИЦиГ СО РАН10.52727/2078-256X-2025-21-3-237-247ateroskleroz-1128Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESАнализ вариантов в генах липидного обмена у лиц молодого возраста 25–44 лет с контрастными уровнями холестерина липопротеинов низкой плотностиAnalysis of lipid metabolism gene variants in individuals aged 25–44 years with contrasting LDL cholesterol levelshttps://orcid.org/0000-0003-4892-0861СпиридоновА. Н.SpiridonovA. N.

Александр Николаевич Спиридонов, аспирант по специальности «Кардиология»

630089, г. Новосибирск, ул. Бориса Богаткова, 175/1

Aleksandr N. Spiridonov, graduate student "Cardiology"

175/1, Boris Bogatkov st., Novosibirsk, 630089

https://orcid.org/0000-0002-0403-545XИванощукД. Е.IvanoshchukD. E.

Динара Евгеньевна Иванощук, научный сотрудник лаборатории молекулярно-генетических исследований терапевтических заболеваний

630089, г. Новосибирск, ул. Бориса Богаткова, 175/1

Dinara E. Ivanoshchuk, researcher at the laboratory of molecular genetic investigations of internal diseases

175/1, Boris Bogatkov st., Novosibirsk, 630089

dinara2084@mail.ruhttps://orcid.org/0000-0003-2268-4186КаштановаЕ. В.KashtanovaE. V.

Елена Владимировна Каштанова, д-р биол. наук, зав. лабораторией клинических биохимических и гормональных исследований терапевтических заболеваний

630089, г. Новосибирск, ул. Бориса Богаткова, 175/1

Elena V. Kashtanova, doctor of biological sciences, head of the laboratory of clinical biochemical and hormonal studies of therapeutic diseases

175/1, Boris Bogatkov st., Novosibirsk, 630089

elekastanova@yandex.ruhttps://orcid.org/0000-0001-6108-1025ШахтшнейдерЕ. В.ShakhtshneiderE. V.

Елена Владимировна Шахтшнейдер, д-р. мед. наук, ведущий научный сотрудник лаборатории молекулярно-генетических исследований терапевтических заболеваний

630089, г. Новосибирск, ул. Бориса Богаткова, 175/1

Elena V. Shakhtshneider, doctor of medical sciences, leadering researcher in the laboratory of the molecular genetic investigations of internal disease

175/1, Boris Bogatkov st., Novosibirsk, 630089

shakhtshneyderv@bionet.nsc.ruНаучно-исследовательский институт терапии и профилактической медицины – филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences202529092025213237247Copyright © Спиридонов А.Н., Иванощук Д.Е., Каштанова Е.В., Шахтшнейдер Е.В., 20252025Спиридонов А.Н., Иванощук Д.Е., Каштанова Е.В., Шахтшнейдер Е.В.Spiridonov A.N., Ivanoshchuk D.E., Kashtanova E.V., Shakhtshneider E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ateroskleroz.elpub.ru/jour/article/view/1128

Рост распространенности гиперхолестеринемии липопротеинов низкой плотности (ЛПНП) и связанных с ней заболеваний среди молодежи является серьезной проблемой для многих стран. Цель исследования – идентифицировать редкие функционально значимые варианты в кодирующих областях и прилегающих сайтах сплайсинга генов, ассоциированных с повышенным уровнем холестерина ЛПНП (ХС ЛПНП), у мужчин и женщин 25–44 лет.Методы. Включенная в исследование популяционная выборка была распределена по децилям на основе концентрации ХС ЛПНП. В исследование включили 146 человек с уровнем ХС ЛПНП ˂ 2,1 ммоль/л, входящих в первый дециль и 158 человек с уровнем ХС ЛПНП ≥ 4,2 ммоль/л, входящих в последний дециль. Выполнено таргетное высокопроизводительное секвенирование.Результаты. В выборке молодых людей у 0,07 % обследованных уровень ХС ЛПНП превышал 8,5 ммоль/л, у 0,13 % обследованных находился в пределах 6,5–8,4 ммоль/л, у 2,25 % – в пределах 5,0–6,4 ммоль/л. В нашем исследовании обследованные с уровнем ХС ЛПНП, соответствующим первому и последнему децилю, различались по спектру вариантов в генах липидного обмена. Функционально значимые варианты, связанные с развитием гиперхолестеринемии ЛПНП, выявлены у молодых людей с уровнем ХС ЛПНП ≥ 4,2 ммоль/л в кодирующих областях генов LDLR и APOB, а также в генах ABCA1, LCAT, LIPA, LIPC, LPA.Заключение. Идентифицированы редкие функционально значимые варианты в кодирующих областях и прилегающих сайтах сплайсинга генов, ассоциированных с повышенным уровнем холестерина ЛПНП, у мужчин и женщин в молодом возрасте.

The increasing prevalence of low-density lipoprotein (LDL) hypercholesterolemia and its associated diseases among young people is a major public health concern in many countries. The aim of this study was to identify rare functionally significant variants in coding regions and adjacent splice sites of genes associated with elevated LDL cholesterol (LDL-C) levels in men and women aged 25–44 years.Methods. A population-based sample was stratified by deciles according to LDL-C concentration. The study included 146 individuals with LDL-C <2.1 mmol/L (first decile) and 158 individuals with LDL-C ≥ 4.2 mmol/L (tenth decile). Targeted high-throughput sequencing was performed.Results. In the sample of young adults, 0.07 % had LDL-C levels >8.5 mmol/L, 0.13 % had levels ranging from 6.5 to 8.4 mmol/L, and 2.25 % had levels between 5.0 and 6.4 mmol/L. Participants in the first and tenth LDL-C deciles differed in the spectrum of variants in lipid metabolism genes. Functionally significant variants associated with LDL hypercholesterolemia were identified in individuals with LDL-C ≥4.2 mmol/L in the coding regions of the LDLR and APOB genes, as well as in ABCA1, LCAT, LIPA, LIPC, and LPA.Conclusions. Rare functionally significant variants in coding regions and adjacent splice sites of genes associated with elevated LDL-C levels were identified in young men and women.

гиперхолестеринемия липопротеинов низкой плотностимолодой возрасттехнология таргетного секвенированияредкие варианты в генах липидного обменасемейная гиперхолестеринемияlow-density lipoprotein hypercholesterolemiayoung agetargeted sequencing technologyrare variants in lipid metabolism genesfamilial hypercholesterolemiaРабота выполнена в рамках государственного задания FWNR-2024-0002.The study was carried out within the framework of the main topic of state assignment No. FWNR-2024-0004.ReferencesWorld Health Organization. Noncommunicable diseases. Available at: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-deathWorld Health Organization. Noncommunicable diseases. 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The authors declare that there are no conflicts of interest present.