medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2021-15-78-87medsovet-6430Research ArticleЗАБОЛЕВАНИЯ БИЛИАРНОЙ СИСТЕМЫ И ПЕЧЕНИDISEASES OF THE BILIARY SYSTEM AND LIVERГенетические предикторы и патофизиологические особенности неалкогольной жировой болезни печениGenetic predictors and pathophysiological features of non-alcoholic fat liver diseasehttps://orcid.org/0000-0003-3992-9207СмирноваО. В.SmirnovaO. V.

д.м.н., доцент, заведующая лабораторией клинической патофизиологии Научно-исследовательского институтамедицинских проблем Севера

660022, Красноярск, ул. Партизана Железняка, д. 3Г

Dr. Sci. (Med.), Associate Professor, Head of the Laboratory of Clinical Pathophysiology, Research Institute of Medical Problemsof the North

3g, Partizan Zheleznyak St., Krasnoyarsk, 660022

ovsmirnova71@mail.ruhttps://orcid.org/0000-0003-4268-6568МоскаленкоО. Л.MoskalenkoO. L.

к.б.н., старший научный сотрудник лаборатории клинической патофизиологии Научно-исследовательскогоинститута медицинских проблем Севера

660022, Красноярск, ул. Партизана Железняка, д. 3Г

Cand. Sci. (Biol.), Senior Researcher, Head of the Laboratory of Clinical Pathophysiology, Research Institute of Medical Problems of the North

3g, Partizan Zheleznyak St., Krasnoyarsk, 660022

gre-ll@mail.ruhttps://orcid.org/0000-0002-5988-1688КаспаровЭ. В.KasparovE. V.

д.м.н., профессор, директор Научно-исследовательского института медицинских проблем Севера

660022, Красноярск, ул. Партизана Железняка, д. 3Г

Dr. Sci. (Med.), Professor, Director Research Institute of Medical Problems of the North

3g, Partizan Zheleznyak St., Krasnoyarsk, 660022

impn@impn.ruКаспароваИ. Э.Kasparova,I. E.

к.м.н., старший научный сотрудник лаборатории клинической патофизиологии

660022, Красноярск, ул. Партизана Железняка, д. 3Г

Cand. Sci. (Med.), Senior Research Laboratory of Clinical Pathophysiology

3g, Partizan Zheleznyak St., Krasnoyarsk, 660022

impn@impn.ruКрасноярский научный центр Сибирского отделения Российской академии наук, Научно-исследовательский институт медицинских проблем СевераРоссияKrasnoyarsk Science Centre of the Siberian Branch of Russian Academy of Science, Scientific Research Institute of Medical Problems of the NorthRussian Federation2021171020210157887Copyright © Смирнова О.В., Москаленко О.Л., Каспаров Э.В., Каспарова И.Э., 20212021Смирнова О.В., Москаленко О.Л., Каспаров Э.В., Каспарова И.Э.Smirnova O.V., Moskalenko O.L., Kasparov E.V., Kasparova, I.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/6430

Неалкогольная жировая болезнь печени (НАЖБП) является ведущей причиной заболеваний печени в высокоразвитых странах. Риск развития НАЖБП и связанных с ней осложнений сильно варьирует среди людей различных национальностей и определяется экологическими и генетическими факторами. Полногеномные исследования выявили устойчивые и воспроизводимые ассоциации между вариациями генов, такими как PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B1 и НАЖБП. В данной статье мы рассматриваем влияние генов и факторов окружающей среды на патофизиологические особенности НАЖБП. Использование достаточной популяционной выборки с анализом массивов SNP и применением методов секвенирования (экзома и генома в  целом) приведет к  обнаружению дополнительных генетических вариантов, неизбежно улучшит понимание патогенеза НАЖБП и позволит разработать технологию персонифицированного риска в оценке заболевания у пациента. Цель исследования  – изучить по  данным литературы генетические предикторы НАЖБП с  интерпретацией проведенных исследований. В настоящее время имеются убедительные доказательства, что конкретные варианты генетического риска оказывают большое влияние на НАЖБП, причем размер их эффекта сопоставим с влиянием основных метаболических факторов риска, таких как ожирение и сахарный диабет 2-го типа. Повышение риска распространяется на возникновение и прогрессирование всего спектра проявлений НАЖБП, включая общую смертность, обусловленную патологией печени. В настоящее время отдельные генетические варианты не позволяют составить персонифицированный профиль риска, в связи с этим наиболее целесообразным подходом является разработка полигенных оценок риска. Количество генетических локусов, связанных с распространенностью и исходами НАЖБП, остается ограниченным. Использование достаточной популяционной выборки с анализом массивов SNP и применением методов секвенирования (экзома и генома в целом) приведет к обнаружению дополнительных генетических вариантов и неизбежно улучшит понимание патогенеза НАЖБП и позволит разработать технологию персонифицированного риска в оценке заболевания.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in highly developed countries. The risk of developing NAFLD and associated complications varies greatly among people of different nationalities and is determined by environmental and genetic factors. Genome-wide studies have revealed strong and reproducible associations between gene variations such as PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B1, and NAFLD. In this article, we consider the influence of genes and environmental factors on the pathophysiological features of NAFLD. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants, will inevitably improve the understanding of the pathogenesis of NAFLD, and will allow the development of a technology for personalized risk in assessing the disease in a patient. The aim of our study was to study the genetic predictors of NAFLD based on literature data with the interpretation of the studies. There is now strong evidence that specific variants of genetic risk have a large effect on NAFLD, and their effect is comparable to that of major metabolic risk factors such as obesity and type 2 diabetes. The increased risk extends to the onset and progression of the entire spectrum of NAFLD manifestations, including overall mortality due to liver disease. Currently, individual genetic variants do not allow the creation of a personalized risk profile; therefore, the most expedient approach today is the development of polygenic risk assessments. The number of genetic loci associated with the prevalence and outcome of NAFLD remains limited. The use of a sufficient population sample with the analysis of SNP arrays and the use of sequencing methods (exome and genome as a whole) will lead to the discovery of additional genetic variants and will inevitably improve the understanding of the pathogenesis of NAFLD and will allow the development of a technology for personalized risk in the assessment of the disease.

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