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UkrainePediatricGlobal

Журнал «Здоровье ребенка» Том 19, №3, 2024

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Генетична схильність до метаболічно асоційованої жирової хвороби печінки

Генетична схильність до метаболічно асоційованої жирової хвороби печінки

Авторы: Абатуров О.Є., Нікуліна А.О.
Дніпровський державний медичний університет, м. Дніпро, Україна

Рубрики: Педиатрия/Неонатология

Разделы: Справочник специалиста

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Резюме

Літературний огляд присвячений висвітленню питання щодо генетичних факторів ризику, що мають зв’язок з розвитком метаболічно асоційованої жирової хвороби печінки (МАЖХП). Генетичні обстеження людини виявили 132 гени, серед яких 32 локуси міцно пов’язані з патогенезом МАЖХП. Встановлено, що ризик розвитку МАЖХП несуть однонуклеотидні варіанти різних генів, продукти яких беруть участь у ліпідному, вуглеводному обміні, підтриманні окиснювально-відновного стану, розвитку запалення й фіброзу тканини печінки, тобто є компонентами МАЖХП-реактому. Автори навели детальний перелік генетичних факторів, окремо виділивши серед них ті, що впливають на ризик виникнення МАЖХП та безпосередньо метаболічно асоційованого стеатогепатиту й фіброзу печінки. Автори акцентували, що саме однонуклеотидні варіанти генів протеїну 3, що містить пататин-подібний фосфоліпазний домен, трансмембранного протеїну 6 — члена суперродини 2 і 17b-гідроксистероїд-дегідрогенази 13-го типу характеризуються найбільш високим ступенем асоціації з МАЖХП (ВР > 1,6) порівняно з однонуклеотидними варіантами інших генів, ідентифікованих за допомогою досліджень генних асоціацій. Поєднання декількох поліморфізмів збільшує ризик розвитку і тяжкого перебігу МАЖХП. Адитивний стеатогенний ефект однонуклеотидних варіантів генів протеїну 3, що містить пататин-подібний фосфоліпазний домен, і трансмембранного протеїну 6 — члена суперродини 2, ймовірно, обумовлений посиленням експресії генів, що беруть участь у ліпогенезі de novo. Автори наголошують на необхідності оцінки генетичного ризику МАЖХП, що має включати молекулярно-генетичні дослідження на ранньому етапі обстеження.

The literature review highlights the issue of genetic risk factors associated with the development of metabolic dysfunction-associated fatty liver disease. Human genetic examinations revealed 132 genes among which 32 loci are strongly associated with the pathogenesis of metabolic dysfunction-associated fatty liver disease. It has been found that the risk of developing metabolic dysfunction-associated fatty liver disease is carried by single-nucleotide variants of various genes whose products are involved in lipid and carbohydrate metabolism, maintenance of the redox state, the development of inflammation and fibrosis of liver tissue, which are components of metabolic dysfunction-associated fatty liver disease reactome. The authors presented a detailed list of genetic factors singling out those that influence the risk of metabolic dysfunction-associated fatty liver disease and directly metabolic dysfunction-associated steatohepatitis and liver fibrosis. Also, they emphasized that it is the single-nucleotide variants of the genes of protein 3 containing a patatin-like phospholipase domain, transmembrane 6 superfamily member 2, and 17b-hydroxysteroid dehydrogenase type 13 that are characte­rized by the highest degree of association with metabolic dysfunction-associated fatty liver disease (odds ratio > 1.6) compared to single-nucleotide variants of other genes identified by gene association studies. The combination of several polymorphisms increases the risk of development and severity of metabolic dysfunction-associated fatty liver disease. The additive steatogenic effect of protein 3 single-nucleotide gene variants containing a patatin-like phospholipase domain and transmembrane 6 superfamily member 2 is probably due to an increased expression of genes involved in de novo lipogenesis. The authors emphasize the need for genetic risk assessment of metabolic dysfunction-associated fatty liver disease, which should include molecular genetic testing at an early stage of examination.


Ключевые слова

метаболічно асоційована жирова хвороба печінки; генетичні фактори ризику; ожиріння; діти

metabolic dysfunction-associated fatty liver disease; genetic disposition; obesity; children

doi: http://dx.doi.org/10.22141/2224-0551.19.3.2024.1696

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