On assessing risks of developing and progressing non-alcoholic fatty liver disease using TNF-α, IL6, and VEGF factors and polymorphisms of their genes
Authors:   Perm State Medical University named after Academician E.A. Wagner, 26 Petropavlovskaya Str., Perm, 614990, Russian Federation, Bulatova I.A. , Pestrenin L.D. ,   Perm State Medical University named after Academician E.A. Wagner, 26 Petropavlovskaya Str., Perm, 614990, Russian Federation, Shevlyukova T.P. ,   Tyumen State Medical University, 54 Odesskaya Str., Tyumen, 625023, Russian Federation, Krivtsov A.V. ,   Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, 82 Monastyrskaya Str., Perm, 614045, Russian Federation, Gulyaeva I.L. ,   Perm State Medical University named after Academician E.A. Wagner, 26 Petropavlovskaya Str., Perm, 614990, Russian Federation
Published: June 2022

Our research aim was to develop a system for calculating risks of development and progression of non-alcoholic fatty liver disease (NAFLD). The system would be based on interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF) and TNF-α gene polymorphism in the region -308G/A (rs1800629), IL-6 in the region –174G/C (rs1800795), and VEGFA in the region –634G/C (rs2010963). We examined 52 patients with NAFLD and 65 healthy donors. The examination involved estimating levels of cytokines TNF-α, IL-6 and VEGF in blood serum. We also studied the polymorphism of the TNF-α genes in the -308G/A region, IL-6 in the -174G/C region, and VEGFA in the -634G/C region. Women aged from 32 to 54 years prevailed among patients with NAFLD (67 %). We established in this research that concentrations of the pro-inflammatory cytokines TNF-α, IL-6 and the level of VEGF in the blood serum were significantly higher in patients with NAFLD than in the reference group (p = 0.03; p = 0.00003 and р = 0.001 accordingly). This confirms an occurring inflammatory syndrome and endothelial dysfunction that are typical for this pathology. Patients with NAFLD tended to have the AA genotype of the TNF-α -308G/A gene (rs1800629) significantly more frequently than healthy donors (р = 0.04). Homozygote CC and allele C of the VEGFA gene (G-634C) in the position rs2010963 were significantly more often detected in the test group (patients with NAFLD) than in the reference one (p = 0.02 and p = 0.01 respectively). We didn’t detect any statistically significant differences in the IL-6 gene polymorphism in the -174G/C (rs1800795) region in the analyzed groups. TNF-α -308G/A gene polymorphism correlated with activating production of TNF-α and IL-6 cytokines (Ki = 0.588; p = 0.043 and Ki = 0.597; p = 0.04, respectively), which can lead to developing immune-inflammatory syndrome in its carriers. When determining genetic profiles, we established that 51 % donors had low risks of NAFLD development whereas the risk was high for 75 % of patients with the disease. The risk of developing NASP is associated with carrying the AA genotype of the TNF-α -308G/A gene and the CC genotype of the VEGFA -634G/C gene. Assessment of a genetic profile using these markers provides an opportunity to assess risks of developing NAFLD in healthy people and to predict its progression in patients with the disease.