Russian Journal of OncologyRussian Journal of OncologyРоссийский онкологический журнал1028-99842412-9119Eco-Vector64339310.17816/onco643393ZMHGKAOriginal Study ArticlesОригинальные исследованияResearch ArticleGenetic determinants of hepatocellular carcinoma: role of PNPLA3, FABP2, FADS1/FADS2 genes in YakutsГенетические детерминанты гепатоцеллюлярной карциномы: роль генов PNPLA3, FABP2, FADS1/FADS2 у якутовhttps://orcid.org/0000-0001-7862-18766167-5254PavlovaNadezhda I.ПавловаНадежда Ивановна
Russian Federation

Cand. Sci. (Biology)

канд. биол. наук

solnishko_84@inbox.ruhttps://orcid.org/0009-0005-5977-55185746-3015KrylovAlexey V.КрыловАлексей Васильевич
Russian Federation
alexkrulovwork@gmail.comhttps://orcid.org/0009-0008-5414-41021853-0018BochurovAlexey A.БочуровАлексей Алексеевич
Russian Federation
binbaher@mail.ruhttps://orcid.org/0000-0001-9782-85653750-7480TroevIvan P.ТроевИван Петрович
Russian Federation
ysumed@yandex.ruhttps://orcid.org/0000-0002-2841-03578254-3787KurtanovKhariton A.КуртановХаритон Алексеевич
Russian Federation

MD, Cand. Sci. (Medicine)

канд. мед. наук

hariton_kurtanov@mail.ruYakut Science Center of Complex Medical ProblemsЯкутский научный центр комплексных медицинских проблемAmmosov North-Eastern Federal UniversityСеверо-Восточный федеральный университет им. М.К. АммосоваRepublican Clinical Hospital No. 3Республиканская клиническая больница № 3, Якутск1009202519102025302Russian Journal of OncologyРоссийский онкологический журнал1141232512202419082025Copyright ©; 2025, Eco-VectorCopyright ©; 2025, Эко-Вектор2025Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0/https://rjonco.com/1028-9984/article/view/643393

BACKGROUND: Hepatocellular carcinoma is an aggressive primary liver cancer. Major risk factors include cirrhosis, hepatitis B and C infections, nonalcoholic fatty liver disease, and type 2 diabetes mellitus. According to state medical statistics of the Russian Federation for 2021, the highest incidence of malignant neoplasms of the liver and intrahepatic bile ducts was reported in the Republic of Sakha (Yakutia). This may be related to dietary changes that have increased the prevalence of obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease.

AIM: The work aimed to investigate the variability of the PNPLA3, FABP2, FADS1, and FADS2 genes, which are involved in lipid metabolism and associated with nonalcoholic fatty liver disease—a risk factor for hepatocellular carcinoma—in the Yakut population.

METHODS: A total of 498 volunteers participated in the study, of whom 126 were diagnosed with nonalcoholic fatty liver disease with concomitant type 2 diabetes mellitus. Single-nucleotide polymorphisms were determined using polymerase chain reaction followed by restriction fragment length polymorphism analysis.

RESULTS: In the examined polymorphisms of the PNPLA3, FADS1, and FADS2 genes, a predominance of alleles pathogenic with respect to nonalcoholic fatty liver disease was found in both groups. For the rs1799883 polymorphism of the FABP2 gene, a significant association of the Ala allele with nonalcoholic fatty liver disease and concomitant type 2 diabetes mellitus was identified (p = 0.02). Compared with other populations from the 1000 Genomes project database, a high frequency of alleles pathogenic with respect to nonalcoholic fatty liver disease was observed in the Yakut population.

CONCLUSION: The high prevalence of PNPLA3, FABP2, FADS1, and FADS2 gene variants associated with increased body mass index and nonalcoholic fatty liver disease is likely related to an adaptive mechanism for fat accumulation in the liver. With the dietary shift from lipid-protein to predominantly carbohydrate intake, these previously advantageous allelic variants now contribute to metabolic disorders that influence the incidence of liver diseases, including hepatocellular carcinoma.

Обоснование. Гепатоцеллюлярная карцинома представляет собой агрессивный первичный рак печени, факторами развития которого являются цирроз печени, инфекции гепатита B и C, неалкогольная жировая болезнь печени (НАЖБП) и, в частности, сахарный диабет 2 типа (СД2). По данным Государственной медицинской статистики Российской Федерации за 2021 г., самая высокая заболеваемость злокачественными новообразованиями печени и внутрипечёночных жёлчных протоков была отмечена в Республике Саха (Якутия), что, возможно, связано с изменением в привычках питания, которое привело к увеличению числа лиц с ожирением, СД2 и НАЖБП.

Цель. Изучение вариабельности генов PNPLA3, FABP2, FADS1 и FADS2, участвующих в липидном обмене и ассоциированных с неалкогольной жировой болезнью печени, фактором риска гепатоцеллюлярной карциномы, в якутской популяции.

Методы. Всего в исследовании приняло участие 498 добровольцев, из которых 126 имели диагноз НАЖБП с сопутствующим СД 2 типа. Однонуклеотидные полиморфизмы определяли методом полимеразной цепной реакции с последующим анализом полиморфизма длин рестрикционных фрагментов.

Результаты. В исследованных полиморфизмах генов PNPLA3, FADS1 и FADS2 выявлено преобладание патологических в отношении к НАЖБП аллелей в обеих группах испытуемых. В отношении полиморфизма rs1799883 гена FABP2 выявлена значимая (р=0,02) связь аллели Ala с НАЖБП с сопутствующим СД2. При сравнении с другими популяциями из базы данных проекта «1000 Genomes» в популяции якутов установлена высокая частота патологических в отношении к НАЖБП аллелей исследованных полиморфизмов.

Заключение. Высокая распространённость вариантов генов PNPLA3, FABP2, FADS1 и FADS2, ассоциированных с повышенным индексом массы тела и НАЖБП, вероятно, связана с адаптивным механизмом к накоплению жира в печени. С изменением липидно-белковой диеты на преимущественно углеводную благоприятные ранее аллельные варианты этих генов сегодня приводят к метаболическим нарушениям, что влияет на заболеваемость патологиями печени, в том числе к гепатоцеллюлярной карциноме.

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