aterosklerozАтеросклерозAteroscleroz2078-256X2949-3633НИИТПМ-филиал ИЦиГ СО РАН10.52727/2078-256X-2024-20-1-6-15ateroskleroz-1023Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПолиморфизмы генов-транспортеров оттока стеролов g5 и g8 АТФ-связывающей кассеты при сердечно-сосудистых заболеваниях и сахарном диабете 2 типаPolymorphisms of the ATP-binding cassette sterol efflux transporter genes g5 and g8 in cardiovascular diseases and type 2 diabetes mellitushttps://orcid.org/0000-0003-0069-7744ГригорьеваИ. Н.Grigor’evaI. N.

Ирина Николаевна Григорьева, д-р мед. наук, проф., главный научный сотрудник, проф. отдела образования

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

Scopus Author ID: 7004630757,

Web of Science Researcher ID JGE-0324-2023

AuthorID: 96089

Irina N. Grigor’eva, doctor of medical sciences, professor, chief researcher

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

Scopus Author ID: 7004630757,

Web of Science Researcher ID JGE-0324-2023

AuthorID: 96089

grigorieva2024@yandex.ruhttps://orcid.org/0000-0002-5786-6927НотоваТ. Е.NotovaT. E.

Татьяна Евгеньевна Нотова, врач-терапевт, гастроэнтеролог

630087, г. Новосибирск, ул. Немировича-Данченко, 130

Tatiana E. Notova, therapist, gastroenterologist

130, Nemirovich-Danchenko str., Novosibirsk, 630087

notovivan007@mail.ruhttps://orcid.org/0000-0001-5809-2241СувороваТ. С.SuvorovaT. S.

Татьяна Станиславовна Суворова, канд. мед. наук, доцент кафедры внутренних болезней

630091, г. Новосибирск, Красный пр., 52

Tatyana S. Suvorova, candidate of medical sciences, associate professor of the department of internal medicine

52, Krasny Prospekt, Novosibirsk, 630091

tatyana.suvorova13@yandex.ruНепомнящихД. Л.NepomnyashchikhD. L.

Давид Львович Непомнящих, д-р мед. наук, проф. кафедры внутренних болезней

630091, г. Новосибирск, Красный пр., 52

David L. Nepomnyashchikh, doctor of medical sciences, professor of the chair for internal medicine of department of general medicine

52, Krasny Prospekt, Novosibirsk, 630091

dln_nco@mail.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»РоссияResearch Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesRussian FederationГосударственная Новосибирская областная клиническая больницаРоссияNovosibirsk State Regional Clinical HospitalRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Новосибирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияNovosibirsk State Medical University of Ministry of Health of Russian FederationRussian Federation202415032024201615Copyright © Григорьева И.Н., Нотова Т.Е., Суворова Т.С., Непомнящих Д.Л., 20242024Григорьева И.Н., Нотова Т.Е., Суворова Т.С., Непомнящих Д.Л.Grigor’eva I.N., Notova T.E., Suvorova T.S., Nepomnyashchikh D.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://ateroskleroz.elpub.ru/jour/article/view/1023

Мутации со снижением экспрессии и функции генов белков АТФ-связывающей кассеты ABCG5 и ABCG8 как основных транспортеров оттока стеролов приводят к накоплению ксеностеролов в плазме, связанному с изменениями липидного профиля, гипергликемией, риском сердечно-сосудистых заболеваний (ССЗ) и сахарного диабета 2 типа (СД2). Приведены результаты исследований роли полиморфизмов генов ABCG5/G8 при ССЗ и СД2. В нескольких исследованиях, в том числе крупномасштабных, доказано влияние вариантов ABCG5/G8 (rs4245791, rs41360247 rs4299376, rs11887534, rs7598542, rs78451356, rs4148217 и др.) на риск развития ишемической болезни сердца (ИБС), в других – при подтверждении связи риска ИБС с полиморфизмом ABCG5 отрицали такой статус для ABCG8. Поскольку нарушения метаболизма стеролов, наблюдаемые у лиц с СД2, вероятно, опосредованы низкой чувствительностью к инсулину, многие авторы подтвердили ассоциацию вариантов rs4299376, rs4148211, rs140231607 и rs6720173 генов ABCG5/G8 с риском развития СД2, другие не обнаружили такой связи с СД2 для вариантов rs4299376, rs11887534 и rs4148217 гена ABCG8. Снижение экспрессии мРНК генов ABCG5/G8 наблюдали при СД2 у экспериментальных животных и у людей; напротив, сверхэкспрессия ABCG5/G8 у мышей db/db восстановила чувствительность печени к инсулину, что привело к снижению уровня глюкозы натощак, липидов и улучшению толерантности к глюкозе. Противоречивость данных о связи полиморфизма генов ABCG5/G8 с риском ССЗ и СД2, вероятно, может быть обусловлена межпопуляционными различиями, что обусловливает необходимость дальнейшего изучения вклада вариантов последовательности генов ABCG5/G8 в риск развития этих заболеваний.

Mutations with a decrease in the expression and function of the of the ATP-binding cassette genes proteins ABCG5 and ABCG8, as the main sterol efflux transporters, lead to the accumulation of xenosterols in plasma associated with changes in the lipid profile, hyperglycemia and the risk of cardiovascular diseases (CVD) and type 2 diabetes mellitus (DM2). The review presents studies of the role of ABCG5/G8 polymorphisms in CVD and DM2. In several studies, including large–scale ones, the influence of ABCG5/G8 variants (rs4245791, rs41360247 rs4299376, rs11887534, rs7598542, rs78451356, etc.) on the risk of coronary heart disease (CHD) was proved, in others – when confirming the association of the risk of CHD with ABCG5 polymorphism, this status for ABCG8 was denied. Since sterol metabolism disorders observed in individuals with DM2 are probably associated with low insulin sensitivity, many authors confirmed the association of variants rs4299376, rs4148211, rs140231607 and rs6720173 of the ABCG5/G8 with the risk of DM2, but some authors did not find such a connection with DM2 for variants rs4299376, rs11887534 and rs4148217 of the ABCG8. A decrease in ABCG5/G8 mRNA expression was observed in DM2 in experimental animals and in humans; on the contrary, overexpression of ABCG5/G8 in db/db mice restored the sensitivity of the liver to insulin, which led to a decrease in fasting glucose, lipids and improved glucose tolerance. The inconsistency of data on the association of ABCG5/G8 gene polymorphism with the risk of CVD and DM2 may probably be due to inter-population differences, which necessitates further study of the contribution of ABCG5/G8 variants to the risk of these diseases.

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The authors declare that there are no conflicts of interest present.