gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLC10.22416/1382-4376-2025-35-2-37-44gastro-j-951Research ArticleОБЗОРЫREVIEWSАссоциация полиморфизма ABCG5 и ABCG8 с желчнокаменной болезнью и раком желчного пузыряAssociation of ABCG5 and ABCG8 Polymorphisms with Gallstone Disease and Gallbladder Cancerhttps://orcid.org/0000-0003-0069-7744ГригорьеваИ. Н.Grigor’evaI. N.

Григорьева Ирина Николаевна — доктор медицинских наук, профессор, главный научный сотрудник

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

Irina N. Grigor’eva — Dr. Sci. (Med.), Professor, Chief Researcher

630089, Novosibirsk, Borisa Bogatkova str., 175/1

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

Нотова Татьяна Евгеньевна — врач-терапевт, гастроэнтеролог

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

Tatiana E. Notova — Therapist, Gastroenterologist

630087, Novosibirsk, Nemirovicha-Danchenko str., 130

notovivan007@mail.ruНепомнящихД. Л.NepomnyashchikhD. L.

Непомнящих Давид Львович — доктор медицинских наук, профессор, профессор кафедры внутренних болезней

630091, г. Новосибирск, Красный проспект, 52

David L. Nepomnyashchikh — Dr. Sci. (Med.), Professor, Professor of the Department of Internal Medicine

630091, Novosibirsk, Krasnyi Avenue, 52

dln_nco@mail.ruНаучно-исследовательский институт терапии и профилактической медицины — филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики СО РАН»РоссияResearch Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of SciencesRussian FederationГГБУЗ Новосибирской области «Государственная Новосибирская областная клиническая больница»РоссияState Novosibirsk Regional Clinical HospitalRussian FederationФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияNovosibirsk State Medical UniversityRussian Federation2025250620253523744Copyright © Григорьева И.Н., Нотова Т.Е., Непомнящих Д.Л., 20252025Григорьева И.Н., Нотова Т.Е., Непомнящих Д.Л.Grigor’eva I.N., Notova T.E., Nepomnyashchikh D.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/951Цель обзора

Цель обзора: анализ роли вариантов нуклеотидной последовательности (ВНП) генов ABCG5 и ABCG8 при желчнокаменной болезни (ЖКБ) и раке желчного пузыря (РЖП).

Основные положения

Основные положения. Транспортеры оттока стеролов ABCG5 и ABCG8 имеют ключевое значение в печеночной секреции и кишечной абсорбции холестерина. ABCG5/G8 представляет собой человеческий ген желчных камней LITH9. Один из основных генетических факторов риска ЖКБ rs11887534 (D19H) ABCG8 как ВНП с «приобретением функции» повышает активность транспортера в 3,2 раза, что приводит к перенасыщению желчи холестерином и увеличению риска ЖКБ. В среднем rs11887534 повышает риск ЖКБ у детей в 4 раза, у взрослых — в 2 раза, что доказано в популяционных полногеномных исследованиях и в метаанализах во всем мире. Наличие аллеля Н D19H (rs11887534) связано с двукратным риском рецидива ЖКБ после холецистэктомии. Результаты исследований связи ЖКБ с другими ВНП генов ABCG8 (T400K, A632V, M429V, C54Y) и ABCG5 (E604Q, R50C) являются противоречивыми.

В популяционных исследованиях rs11887534 связан с 4-кратным повышением риска РЖП, причем риск более выражен (в 4,9 раза) у больных РЖП с камнями в желчном пузыре. Мы не обнаружили исследований ВНП генов ABCG5 и ABCG8 при билиарной патологии в России.

Заключение

Заключение. В большинстве исследований подтверждена роль rs11887534 гена ABCG8 как предиктора ЖКБ и РЖП, однако требуются реплицирующие исследования ВНП генов ABCG5 и ABCG8 при билиарной патологии в России.

Aim

Aim: to analyze the role of nucleotide sequence variants (NSVs) of ABCG5 and ABCG8 genes in gallstone disease (GSD) and gallbladder cancer (GBC).

Key points

Key points. ABCG5 and ABCG8 are key sterol efflux transporters that regulate hepatic secretion and intestinal absorption of cholesterol. ABCG5/G8 is the human LITH9 gallstone gene. One of the major genetic risk factors for GSD rs11887534 (D19H) ABCG8, as a ‘gain-of-function’ NSV, increases the activity of this transporter by 3.2 times, which leads to supersaturation of bile with cholesterol and an increased risk of GSD. On average, rs11887534 increases

the risk of GSD in children by 4 times, in adults — by 2 times, which has been proven in population, genome-wide studies and meta-analyses worldwide. The presence of the H allele D19H (rs11887534) is associated with a two-fold risk of recurrence of GSD after cholecystectomy. The results of the studies of the associations of GSD with other NSVs of ABCG8 (T400K, A632V, M429V, C54Y) and ABCG5 (E604Q, R50C) genes are contradictory.

In population studies, rs11887534 was associated with a 4-fold increase in the risk of GBC, and the risk is more prominent (4.9 times) in patients with GBC and gallstones. We found no studies of the NSVs of the ABCG5 and ABCG8 genes in biliary pathology in Russia.

Conclusion

Conclusion. Most studies confirm the role of the rs11887534 ABCG8 gene as a predictor of GSD and GBC; however, replicating studies of NSVs of ABCG5 and ABCG8 genes in biliary pathology in Russia are needed.

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