diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM12744diaendo-12744Research ArticleОбзорыReviewРоль генетических и средовых факторов в детерминации ответа на метформинRole of Genetic and Environmental Factors in Determining the Response to Metforminhttps://orcid.org/0000-0003-3824-3641КучерА. Н.KucherА. N.

Кучер Аксана Николаевна, д.б.н., профессор

Researcher ID: A-7789-2014

Scopus Author ID: 7004507293

SPIN: 5251-2055

634050, Томск, Набережная р. Ушайки, д. 10

 

 

Aksana N. Kucher, PhD in Biology, Professor

Researcher ID: A-7789-2014

Scopus Author ID: 7004507293

SPIN: 5251-2055

10 Ushaika river embankment, 634050 Tomsk

 

aksana.kucher@medgenetics.ruhttps://orcid.org/0000-0001-6133-8986БабушкинаН. П.BabushkinaN. P.

Бабушкина Надежда Петровна, к.б.н. 

Researcher ID: B-3106-2014

Scopus Author ID: 39961071300

SPIN: 4639-1490

Томск

Nadezhda P. Babushkina, PhD in Biology

Researcher ID: B-3106-2014

Scopus Author ID: 39961071300

SPIN: 4639-1490

Tomsk

nad.babushkina@medgenetics.ruНИИ медицинской генетики, Томский национальный медицинский исследовательский центрРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical CenterRussian Federation202115102021246571582Copyright © Кучер А.Н., Бабушкина Н.П., 20222022Кучер А.Н., Бабушкина Н.П.Kucher А.N., Babushkina N.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/12744

Метформин является одним из наиболее часто назначаемых для лечения и профилактики сахарного диабета 2 типа (СД2) лекарственных препаратов. Накапливаются многочисленные свидетельства, указывающие, что в основе неблагоприятных побочных эффектов метформина, а также индивидуальных различий ответа пациентов на лечение лежат как генетические, так и средовые факторы. В настоящем обзоре обобщена информация о генетических факторах и средовых модификаторах, определяющих индивидуальную реакцию пациентов на лечение метформином. Обобщены данные о роли полиморфизма наиболее значимых генов и кодируемых ими белковых продуктов как в развитии неблагоприятных эффектов, так и в определении терапевтического ответа, а также обсуждено место метформина в реализации фенотипических эффектов данных генов.Рассмотрены эндогенные условия и экзогенные воздействия, модифицирующие ответ на метформин. Среди них факторы, влияющие на функциональное состояние генома (уровень метилирования генов, так или иначе связанных с ответом на метформин, и др.), отражающие биологические особенности организма (половая принадлежность, возраст), уровень здоровья (наличие сопутствующих заболеваний, обеспеченность организма биометаллами и витаминами), прием других лекарственных препаратов и т.д. Таким образом, существует широкий спектр модифицирующих ответ на метформин факторов, которые, в отличие от генетических особенностей, являются в большинстве своем управляемыми. При этом и генетические, и средовые факторы могут различаться по значимости в разных этно-территориальных группах населения. Данную информацию необходимо принимать во внимание при разработке персонализированного подхода к назначению метформина для лечения СД2, а также при рекомендации его использовать для лечения других болезней.

Metformin is one of the most commonly prescribed drugs for the treatment and prevention of type 2 diabetes mellitus (T2DM). Numerous evidence accumulates indicating that both genetic and environmental factors underlie adverse side effects of metformin, as well as individual differences in patient response to treatment The present review summarizes information on genetic factors and environmental modifiers determining patients’ individual response to metformin treatment. The data on the role of polymorphism of the most significant genes and protein products encoded by them both in the development of adverse effects and in determining the therapeutic response are summarized, and the place of metformin in the realization of the phenotypic effects of these genes is discussed.Endogenous conditions and exogenous effects modifying the response to metformin are considered. Among them are factors that affect the functional state of the genome (the level of methylation of genes, one way or another associated with the response to metformin, etc.), reflecting the biological characteristics of the organism (gender, age), health level (the presence of concomitant diseases, the supply of biometals and vitamins), taking other medications, etc. Thus, there is a wide range of factors modifying the response to metformin, which, unlike genetic characteristics, are largely controllable. At the same time, both genetic and environmental factors may differ in significance in different ethno-territorial groups of the population. This information should be taken into account when developing a personalized approach to prescribing metformin for the treatment of type 2 diabetes, as well as when recommending its use for the treatment of other diseases.

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