Genetic determinants of hepatocellular carcinoma: the role of PNPLA3, FABP2, FADS1/FADS2 genes in yakuts



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Abstract

BACKGROUND: Hepatocellular carcinoma is an aggressive primary liver cancer, the development factors of which are liver cirrhosis, hepatitis B and C infections, non-alcoholic fatty liver disease (NAFLD) and, in particular, type 2 diabetes mellitus (T2DM). According to the state medical statistics of the Russian Federation for 2021, the highest incidence of malignant neoplasms of the liver and intrahepatic bile ducts was in the Sakha Republic (Yakutia), which is possibly due to a change in eating habits that led to an increase in the number of people with obesity, T2DM and NAFLD.

AIM: To study the variability of the PNPLA3, FABP2, FADS1 and FADS2 genes involved in lipid metabolism and associated with non-alcoholic fatty liver disease, a risk factor for hepatocellular carcinoma in the Yakut population.

METHODS: A total of 498 volunteers participated in the study, of which 126 were diagnosed with NAFLD with concomitant type 2 diabetes. Single nucleotide polymorphisms were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis.

RESULTS: The studied polymorphisms of the PNPLA3, FADS1 and FADS2 genes showed a predominance of alleles pathological in relation to NAFLD in both groups of subjects. With regard to the rs1799883 polymorphism of the FABP2 gene, a reliable (p=0.02) association of the Ala allele with NAFLD with concomitant type 2 diabetes was revealed. When compared with other populations from the 1000 Genomes project database, a high frequency of alleles of the studied polymorphisms pathological in relation to NAFLD was established in the Yakut population.

CONCLUSION: The high prevalence of PNPLA3, FABP2, FADS1 and FADS2 gene variants associated with increased BMI and NAFLD is probably related to an adaptive mechanism for fat accumulation in the liver. With the change in lipid-protein diet to a predominantly carbohydrate diet, previously favorable allelic variants of these genes now lead to metabolic disorders, which affects the incidence of liver pathologies, including hepatocellular carcinoma.

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About the authors

Nadezhda I. Pavlova

Yakut Science Center of Complex Medical Problems, Yakutsk, Russia

Email: solnishko_84@inbox.ru
ORCID iD: 0000-0001-7862-1876
SPIN-code: 6167-5254

Cand. Sci. (Biology)

Russian Federation, Yakutsk, Russia

Alexey V. Krylov

Yakut Science Center of Complex Medical Problems, Yakutsk, Russia

Email: alexkrulovwork@gmail.com
ORCID iD: 0009-0005-5977-5518
SPIN-code: 5746-3015

Resercher Assistant

Russian Federation, Yakutsk, Russia

Alexey A. Bochurov

Yakut Science Center of Complex Medical Problems, Yakutsk, Russia

Email: binbaher@mail.ru
ORCID iD: 0009-0008-5414-4102
SPIN-code: 1853-0018

Resercher Assistant

Russian Federation, Yakutsk, Russia

Ivan P. Troev

Ammosov North-Eastern Federal University, Yakutsk, Russia

Email: ysumed@yandex.ru
ORCID iD: 0000-0001-9782-8565
SPIN-code: 3750-7480

Senior Researcher

Russian Federation, Yakutsk, Russia

Khariton A. Kurtanov

Republican Clinical Hospital No. 3, Yakutsk, Russia

Author for correspondence.
Email: Sydlub@mail.ru
ORCID iD: 0000-0002-2841-0357
SPIN-code: 8254-3787

MD, Cand. Sci. (Medicine)

Russian Federation, Yakutsk, Russia

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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