fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2022-7-2-112-124fcmedicine-555Research ArticleОБЗОРНЫЕ СТАТЬИREVIEW ARTICLESВклад полиморфных вариантов гена транскрипционного фактора NFKB1 в развитие многофакторных заболеваний с воспалительным компонентомContribution of polymorphic variants of the NFKB1 transcription factor gene to the development of multifactorial diseases with an infammatory componenthttps://orcid.org/0000-0001-9952-7854МейерА. В.MeyerA. V.

Мейер Алина Викторовна, кандидат биологических наук, доцент кафедры молекулярной и клеточной биологии

650056, г. Кемерово, ул. Ворошилова, д. 22а

Dr. Alina V. Meyer, PhD, Associate Professor of the Department of Molecular and Cellular Biology

22а, Voroshilova Street, Kemerovo, 650056

shapo-alina@yandex.ruhttps://orcid.org/0000-0003-4645-7009ТолочкоТ. А.TolochkoT. A.

Толочко Татьяна Андреевна, старший преподаватель кафедры морфологии и судебной медицины

650056, г. Кемерово, ул. Ворошилова, д. 22А

Tatiana A. Tolochko, Senior Lecturer, Department of Morphology and Forensic Medicine

22а, Voroshilova Street, Kemerovo, 650056

https://orcid.org/0000-0002-5841-6311АстафьеваЕ. А.AstafyevaE. A.

Астафьева Евгения Анатольевна, ассистент кафедры морфологии и судебной медицины

650056, г. Кемерово, ул. Ворошилова, д. 22А

Eugeniya A. Astaf’eva, Assistant, Department of Morphology and Forensic Medicine

22а, Voroshilova Street, Kemerovo, 650056

https://orcid.org/0000-0002-7945-566XУльяноваМ. В.UlyanovaM. V.

Ульянова Марина Владиславовна, кандидат биологических наук, доцент кафедры молекулярной и клеточной биологии

650056, г. Кемерово, ул. Ворошилова, д. 22А

Dr. Marina V. Ulyanova, PhD, Associate Professor of the Department of Molecular and Cellular Biology

22а, Voroshilova Street, Kemerovo, 650056

https://orcid.org/0000-0002-0927-4855ИмекинаД. О.ImekinaD. O.

Имекина Дарья Олеговна, ассистент кафедры молекулярной и клеточной биологии

650056, г. Кемерово, ул. Ворошилова, д. 22А

Darya O. Imekina, Assistant, Department of Molecular and Cellular Biology

22а, Voroshilova Street, Kemerovo, 650056

https://orcid.org/0000-0003-1593-0676ЛавряшинаМ. Б.LavryashinaM. B.

Лавряшина Мария Борисовна, доктор биологических наук, доцент, заведующая кафедрой молекулярной и клеточной биологии

650056, г. Кемерово, ул. Ворошилова, д. 22А

Dr. Marya B. Lavryashina, Doctor of Biological Science, Head of Department of Molecular and Cellular Biology

22а, Voroshilova Street, Kemerovo, 650056

ФГБОУ ВО «Кемеровский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияKemerovo State Medical UniversityRussian Federation20222806202272112124Copyright © Мейер А.В., Толочко Т.А., Астафьева Е.А., Ульянова М.В., Имекина Д.О., Лавряшина М.Б., 20222022Мейер А.В., Толочко Т.А., Астафьева Е.А., Ульянова М.В., Имекина Д.О., Лавряшина М.Б.Meyer A.V., Tolochko T.A., Astafyeva E.A., Ulyanova M.V., Imekina D.O., Lavryashina M.B.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/555

NFKB1 – продукт одноименного гена – транскрипционный фактор, регулирующий экспрессию генов-мишеней, кодирующих широкий спектр белков с важными для функционирования организма свойствами. Многочисленными исследованиями подтверждается вклад полиморфизма гена NFKB1 в процессы адаптации к климатогеографическим условиям, защиту от инфекционных агентов, а также патогенез многофакторных заболеваний. В материалах статьи обобщаются результаты опубликованных популяционно-генетических и когортных исследований в отношении гена NFKB1. Сводные данные о частотах аллелей гена NFKB1 (rs28362491, rs230521, rs4648068, rs3774937, rs3774959) у населения Европы, Африки, Южной и Восточной Азии, Америки, Востока России и Сибири (по данным открытых баз данных проектов 1000 Genomes и Siberian) иллюстрируют выраженную генетическую дифференциацию мировых популяций по полиморфным вариантам NFKB1, что косвенно подтверждает их селективную роль. Значимость выше перечисленных полиморфизмов в этиологии и патогенезе ряда социально-значимых нозологических форм изучена на основе анализа материалов статей, размещенных на платформе NCBI за период 2008–2021гг. В результате деконструкции данных литературы установлено, что изменения структуры промотора (del) и интронов (SNP-полиморфизм) способны модифицировать активность транскрипционного фактора NFKB1 через изменение экспрессии гена и активности его продукта. Данные литературы формируют неоднозначную картину ассоциаций полиморфных вариантов гена NFKB1 с онкологическими (рак яичников, желудка, молочной железы, мочевого пузыря, колоректальный рак, лимфома Ходжкина, меланома), сердечно-сосудистыми (ишемическая болезнь сердца, острый коронарный синдром, инфаркт миокарда, варикозная болезнь), аутоиммунными и хроническими воспалительными заболеваниями (ожирение, хронический гепатит, ревматоидный артрит, болезнь Бехчета, псориаз, реакции острого воспаления на трансплантат). Неоднозначность установленных ассоциативных связей может быть обусловлена модифицирующим влиянием этнических и популяционных особенностей, а также интенсивностью воздействия флогогенных факторов. Тем не менее, публикуемые в материалах статьи сформированные сводные данные и обобщения могут быть использованы при разработке стратегии фундаментальных и скрининговых исследований в контексте этиологии и патогенеза многофакторных болезней.

NFKB1 — a product of the same-name gene – is a transcription factor that regulates the expression of target genes which encode a wide range of proteins with properties essential for functioning of the body. Numerous studies confrmed the NFKB1 gene's contribution of the polymorphism to the processes of adaptation to climatic and geographical conditions, protection from infectious agents, as well as the pathogenesis of multifactorial diseases. In the materials supplied with the article is a summary of the results of published population-genetic and cohort studies of NFKB1. Summary data on the requencies of NFKB1 gene alleles (rs28362491, rs230521, rs4648068, rs3774937, rs3774959) in the population of Europe, Africa, South and East Asia, America, Eastern Russia and Siberia (according to the open databases from 1000 Genomes and Siberian projects) illustrates the pronounced genetic differentiation of world populations by polymorphic variants of NFKB1, which indirectly confrms their selective role. The signifcance of the aforementioned polymorphisms in the etiology and pathogenesis in a number of socially signifcant nosological forms was studied according to an analysis of materials from articles posted on NCBI platform from 2008 to 2021. As a result of deconstructing the data, it was found that changes in the structure of the promoter (del) and introns (SNP polymorphism) are able to modify the activity of the transcription factor NFKB1, through a change in the expression of the gene and the activity of its product. This information forms an ambiguous picture of associations of the NFKB1 gene polymorphic variants with oncological (ovarian, stomach, breast, bladder, colorectal cancer, Hodgkin's lymphoma, melanoma), cardiovascular (coronary heart disease, acute coronary syndrome, myocardial infarction, varicose veins), autoimmune and chronic infammatory diseases (obesity, chronic hepatitis, rheumatoid arthritis, Behcet's disease, psoriasis, acute infammatory reactions to the graft). Ambiguity of the established associative relations could be due to the modifying infuence of ethnic and population characteristics, as well as intensity of the infuence of phlogogenic factors. Nevertheless, the summarized data and generalizations published in the materials of the article can be used in development of a strategy for basic and screening studies in context of the etiology and pathogenesis of multifactorial diseases.

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