PNPLA3 gene polymorphism impact on the nonalcoholic fatty liver disease course

K.L. Raikhelson¹, V.P. Kovyazina¹, D.V. Sidorenko², V.D. Nazarov², S.V. Lapin², V.L. Emanuel², N.V. Marchenko¹, L.K. Palgova¹,
E.A. Kondrashina¹, A. Yu. Baranovsky¹

¹Saint Petersburg State University

²Pavlov First St. Petersburg State Medical University

Aim: to assess the PNPLA3 I148M gene polymorphism impact on the nonalcoholic fatty liver disease (NAFLD) course in St. Petersburg residents.

Patients and Methods: the study included 60 patients (women — 31, men — 29) aged 29 to 83 years with an established diagnosis of NAFLD. Standard laboratory and instrumental studies were performed, as well as an assessment of hepatic structural changes using transient elastography with controlled attenuation parameter (CAP). The PNPLA3 I148M (rs738409 C>G) gene polymorphism was determined in saliva samples of patients by real-time PCR.

Results: the PNPLA3 homozygous genotype mutation (group 1) was detected in 8 people (13.3%), heterozygous genotype (group 2) — in 29 people (48.3%), no mutation (group 3) — in 23 people (38.3%). There were no statistically significant differences between the study groups in assessing the main parameters of the metabolic syndrome. Elevated alanine aminotransferase (ALT) level was more common in the presence of pathological I148M allele (PNPLA3 gene) (p<0.05). Homozygotes had a higher ALT level vs. carriers of the heterozygous genotype mutation and without it (p<0.05). The average CAP in group 1 was 321±30.8 dB/m, in group 2–295.8±37.5 dB/m, in group 3–287.5±22.5 dB/m. Thus, in the PNPLA3 homozygous genotype mutation, higher rates of hepatic steatosis were revealed vs. patients without the mutation (p<0.05).

Conclusion: in patients (from St. Petersburg) with NAFLD, the PNPLA3 gene polymorphism leads to a more aggressive disease course, manifested by the laboratory cytolysis syndrome and severe hepatic steatosis pathogenesis, especially with the homozygous mutation. Further study of large patient cohorts and different populations will clarify these data and possibly develop screening methods that allow timely detection of high-risk patients of adverse NAFLD course.

Keywords: PNPLA3 gene, nonalcoholic fatty liver disease, fibrosis, steatosis.

For citation: Raikhelson K.L., Kovyazina V.P., Sidorenko D.V. et al. PNPLA gene polymorphism impact on the nonalcoholic fatty liver disease course. RMJ. 2019;12:85–88.