On assessing risks of developing and progressing non-alcoholic fatty liver disease using TNF-α, IL6, and VEGF factors and polymorphisms of their genes

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UDC: 
616.36-003.826-036.17-036.3-079.3: 577.21
DOI: 
10.21668/health.risk/2022.1.12.eng
Authors: 

I.A. Bulatova1, L.D. Pestrenin1, T.P. Shevlyukova3, A.V. Krivtsov2, I.L. Gulyaeva1

Organization: 

1Perm State Medical University named after Academician E.A. Wagner, 26 Petropavlovskaya Str., Perm, 614990, Russian Federation
2Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, 82 Monastyrskaya Str., Perm, 614045, Russian Federation
3Tyumen State Medical University, 54 Odesskaya Str., Tyumen, 625023, Russian Federation

Abstract: 

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.

Keywords: 
non-alcoholic fatty liver disease, cytokines, tumor necrosis factor alpha, interleukin-6, vascular endothelial growth factor, gene polymorphism
Bulatova I.A., Pestrenin L.D., Shevlyukova T.P., Miftakhova A.М., Krivtsov A.V., Gulyaeva I.L. On assessing risks of developing and progressing non-alcoholic fatty liver disease using TNF-α, IL-6, and VEGF factors and polymorphisms of their genes. Health Risk Analysis, 2022, no. 1, pp. 104–112. DOI: 10.21668/health.risk/2022.1.12.eng
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Received: 
28.01.2022
Approved: 
04.03.2022
Accepted for publication: 
11.03.2022

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