aterosklerozАтеросклерозAteroscleroz2078-256X2949-3633НИИТПМ-филиал ИЦиГ СО РАН10.52727/2078-256X-2023-19-1-47-56ateroskleroz-889Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWSПолиморфизм гена аполипопротеина Е, желчнокаменная болезнь, сахарный диабет 2 типа и нарушения липидного обменаApolypoprotein E gene polymorphism, gallstone disease, diabetes 2 type and lipid metabolism disordershttps://orcid.org/0000-0003-0069-7744ГригорьеваИ. Н.Grigor’evaI. N.

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

Scopus Author ID: 7004630757

Web of Science Researcher ID AAF-9998-2020

AuthorID: 96089

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

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

Scopus Author ID: 7004630757

Web of Science Researcher ID AAF-9998-2020

AuthorID: 96089

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

igrigorieva@ngs.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.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 Institutе of Internal and Preventive Medicine – Branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesГосударственная Новосибирская областная клиническая больницаNovosibirsk State Regional Clinical Hospital2023050420231914756Copyright © Григорьева И.Н., Нотова Т.Е., 20232023Григорьева И.Н., Нотова Т.Е.Grigor’eva I.N., Notova T.E.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/889

Цель исследования – проанализировать ассоциацию полиморфизма гена аполипопротеина Е (АРОЕ) с желчнокаменной болезнью (ЖКБ) и сахарным диабетом 2 типа (СД2) и его роль в липидном обмене. Носители аллеля АРОЕ4 имеют самый высокий уровень холестерина в плазме и желчи и наименьшее содержание желчных кислот в желчи, чем носители других аллелей. При ЖКБ обнаружена более высокая частота носителей аллеля АРОЕ4 (в 2,6 раза по сравнению с контролем). Риск ЖКБ снижался на 12 % у носителей аллеля АРОЕ2 по сравнению с носителями АРОЕ3/3. Наши 20-летние исследования подтверждают связь полиморфизма гена APOE и ЖКБ. Частота генотипа ε4/ε4 больше у лиц 18–35 лет с семейным анамнезом ЖКБ (5,8 %) по сравнению с популяцией Новосибирска (1,8 %, р < 0,05). Желчь более литогенна у носителей аллеля АРОЕ4 с ЖКБ: уровень холестерина в их желчи 8,0 ± 0,5 г/л, при генотипе ε2/ε3 – 6,9 ± 0,6 г/л. Холатохолестериновый коэффициент у носителей аллеля АРОЕ4 с семейным анамнезом ЖКБ составляет 6,4 ± 0,7, в его отсутствие – 12,9 ± 0,2 (p < 0,05). У женщин с артериальной гипертензией наличие ЖКБ ассоциировано с содержанием холестерина липопротеинов низкой плотности (ЛПНП) > 3,5 ммоль/л и носительством аллеля АРОЕ3. СД2 является признанным фактором риска ЖКБ. Наиболее распространено мнение, что аллель ε4 представляет собой независимый фактор риска СД2, некоторые авторы считают таковым аллель АРОЕ3. Кроме того, у больных СД2 с генотипом ε3/ε4 отмечалось повышение уровня общего холестерина, холестерина ЛПНП и холестерина, не ассоциированного с липопротеинами высокой плотности, по сравнению с лицами с генотипом ε3/ε3. Другие исследования не обнаружили связи между полиморфизмом гена APOE и ЖКБ или СД2. Противоречивость данных можно объяснить неоднородностью включенных групп и методов генотипирования АРОЕ, что требует дальнейших исследований.

Aim of the study was to explore the impact of apolipoprotein E (APOE) gene polymorphisms (GP) on gallstone disease (GSD) and type 2 diabetes mellitus (DM2) and its role in lipid metabolism. APOE4 allele carriers had the highest levels of plasma and bile cholesterol and the lowest levels of bile acids in bile than other alleles. In GSD a higher frequency of APOE4 carriers (2.6 times compared to control) was found. GSD risk was reduced by 12 % in APOE2 carriers compared to APOE3/3. Our 20-year research confirms the association of APOE GP and GSD. The frequency of ε4/ε4 genotype is higher in people aged 18–35 years with a family history of GSD (5.8 %) compared to population of Novosibirsk (1.8 %, p < 0.05). The bile was more lithogenic in APOE4 carriers with GSD: the bile cholesterol level is 8.0 ± 0.5 versus 6.9 ± 0.6 g/l in ε3/ε3 genotype. APOE4 carriers with a family history of GSD had cholate-cholesterol ratio of 6.4 ± 0.7 versus 12.9 ± 0.2 (p < 0.05) in the absence of APOE4. in women with hypertension, the presence of GSD was associated with a combination of low density cholesterol (LDL-C) > 3.5 mmol/l and the APOE4 carriage. DM2 is a recognized risk factor for GSD. The most common opinion is that the ε4 allele is an independent risk of DM2, some authors consider the allele APOE2. Moreover, DM2 patients with the ε3/ε4 genotype have an increase in total cholesterol, LDL-C and non-high-density lipoprotein cholesterol compared to ε3/ε3. Other studies have not found any associations between APOE GP and GSD or DM2. The inconsistency of the data can be explained by the heterogeneity of the included groups and methods of APOE genotyping, which requires further research.

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