Virtual Conference
Pharma Conference 2022

O.S. Arisheva

RUDN University, Russian Federation

Title: Association of SNPs in the Promoter Regions of VEGF (rs699947 ? rs2010963), ICAM1 (rs281437) and ET-1 (rs1800541) with Serum Levels of Related Proteins and Alcoholic Liver Cirrhosis Risk

Abstract

Introduction: Uncontrolled alcohol addiction can result in liver cirrhosis, manifested by fibrosis with regenerative nodules, portal hypertension, and liver dysfunction. In patients with hepatic endothelium dysfunction and portal hypertension the increased level of endothelium molecules: vasculoendothelial growth factor A (VEGF-A), a soluble form of intercellular adhesion molecule (s-ICAM-1) and endothelin-1 (ET-1), were observed. In alcoholic liver cirrhosis (ALC) elevated levels of VEGF-A, s-ICAM-1 and ET-1 may be associated with the structure of polymorphic loci, the promoter regions of the respective genes, which in turn may be a genetic risk factor for developing liver cirrhosis. The aim was to investigate the relationship between carriage of variant forms of polymorphic loci located in promoter regions of VEGF-A, ICAM-1 and ET-1, with levels of corresponding proteins in blood serum and risk of ALC development.

Methods:
The main group consisted of patients with ALC (n=60). In the control group we included alcohol-dependent individuals without liver pathology (AZ; n=24). The serum levels of VEGF-A, s-ICAM-1, ET-1 were assessed by enzyme immunoassay. The distribution of variant forms of polymorphic loci located in the promoter regions of VEGF-A (rs699947 and rs2010963), ICAM1 (rs281437) and ET-1 (rs1800541) genes in the study sample was performed using real-time polymerase chain reaction.

Results:
  In patients with ALC higher serum levels of VEGF-A, s-ICAM-1, and ET-1 were observed (901.6 [420.6; 1264.1] pg/mL, 970.0 [635; 1129] ng/mL, 1.6 [1.1; 2.8] fmol/mL), compared with AZ (359.4 [251.9; 452.1] pg/mL, 273.0 [172; 415] ng/mL, 1.02 [0; 1.06] fmol/mL). Direct correlations were found between values of serum VEGF-A (r=0.32), s-ICAM-1 (r=0.53), and ET-1 (r=0.58) concentration and portal vein diameter in group with ALC. Patients with ALC were more frequently carriers of the G allele of the rs1800541 locus located in the ET-1 gene promoter compared with AZ group patients (n = 21 (20.2%) versus n = 4 (8.3%), respectively, p = 0.035). In patients with alcohol dependence without liver pathology the G allele of the rs1800541 locus located in the ET-1 gene promoter was associated with an increased risk of ALC development (OR 3.67 (1.18-11.45)). Carriage of allele C of locus rs699947 as well as allele C of locus rs2010963 located in VEGF gene promoter was associated with increased level of VEGF-A in ADCs compared with carriers of this allele in AZ group (p=0.03).

Conclusion: 
Carriage of allele G of locus rs1800541 (ET-1) is a risk factor for ALC development in patients with alcoholic dependence with liver pathology. Carriage of allele C of locus rs699947 as well as allele C of locus rs2010963 located in VEGF gene promoter could determine elevated serum VEGF-A level in ALC.

Biography

She was trained in clinical residency and postgraduate studies at the Department of Faculty Therapy of the Medical Faculty of the Peoples' Friendship University of Russia. She defended her Ph.D. thesis in 2006. She is an employee of the department, conducts teaching, scientific and medical work. She is the author of more than 100 scientific articles and educational and methodical works. She is proficient in ultrasound methods of non-invasive diagnostics of liver fibrosis, methods of molecular genetic diagnostics. She has 18 years of experience in clinical research and treatment of patients with chronic liver disease.