Еffect of PNPLA3, SERPINA1 and HFE genes polymorphisms on the course of nonalcoholic fatty liver disease


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Abstract

Introduction: nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. But it remains unclear what factors influence the progression of the disease. It is interesting to study the influence of the genetic aspect on the course of NAFLD. The aim of the study: to investigate the influence of PNPLA3, SERPINA1, HFE gene polymorphisms on the development of NAFLD. Methods: 59 NAFLD patients were examined. Anthropometric data and biochemical indices were assessed. Hereditary liver diseases were excluded. The degree of steatosis and the stage of hepatic fibrosis were assessed using transient elastometry on a Fibroscan. Genotyping of point mutations in genes PNPLA3 (rs738409), SERPINA1 (rs17580 and rs28929474) and HFE (rs1799945, rs1800730 and rs1800562) was performed by real-time PCR. Results: polymorphisms in the PNPLA3 gene were found in 61%, in the SERPINA1 gene - in 10.2%, and in the HFE gene - in 28.8% of cases. In carriers of the I148Mpolymorphism of the PNPLA3 gene the ALT level was significantly higher in the comparison groups ofhetero- and homozygous carriers and the normal genotype (p=0.012 and p=0.017). The AST level was also significantly higher in carriers of the MZ genotype of the SERPINA1 gene (p=0.049). The ALT level was higher in carriers of the H63D and C282Ypolymorphisms of the HFE gene compared with the normal genotype (p=0.02 and p=0.03). The same relationship was demonstrated for carriers of C282Y and AST level (p=0.017). When assessing the level of steatosis, the average CAP was higher in the group of homozygous carriers ofI148M of the PNPLA3 gene (p=0.045) and carriers of polymorphism C282Y (p=0.021) compared with the normal genotype. Authors found no relationship between pathological polymorphisms in the PNPLA3, SERPINA1, and HFE genes and the severity of fibrotic changes. Patients with a BMI > of 35 kg/m2 had a higher liver fibrosis rate (p=0.037). Conclusion: the presence ofpolymorphisms of the PNPLA3, SERPINA1, and HFE genes in NAFLD is associated with an increase in laboratory markers of hepatocellular damage, as well as the severity of hepatic steatosis.

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About the authors

Darya Vladimirovna Sidorenko

Pavlov First Saint Petersburg State Medical University

Email: si-do-renko@mail.ru
medical resident

Vladimir Dmitrievich Nazarov

Pavlov First Saint Petersburg State Medical University

Email: nazarov19932@mail.ru
junior researcher

Sergey Vladimirovich Lapin

Pavlov First Saint Petersburg State Medical University

Email: svlapin@mail.ru
Head of the Laboratory.

Vladimir Leonidovich Emanuel

Pavlov First Saint Petersburg State Medical University

Email: vladimirem1@gmail.com
Head of the Department.

Karina Leonidovna Raikhelson

Saint Petersburg State University

Email: kraikhelson@mail.ru
Professor. Scientific and Educational Center of Gastroenterology and Hepatology

Veronika Pavlovna Kovyazina

Saint Petersburg State University

senior laboratory assistant. Scientific and Educational Center of Gastroenterology and Hepatology

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