The association of VWF (T2385C) and VEGFA (G634C) gene polymorphism with the development of non-alcoholic hepatic steatosis in obese women during menopause

Abstract

Non-alcoholic hepatic steatosis (NAHS) is the most common clinical and morphological variant of non-alcoholic fatty liver disease. The pathogenesis of NAHS is multifactorial. Alterations of intrahepatic hemodynamics associated with liver pathology often result in damage to the endothelial lining of sinusoids and endothelial dysfunction. In recent years, the interest of researchers in assessing the role of genetic factors in the development and progression of diseases has increased. Аim: To determine the blood concentrations of vascular endothelial growth factor (VEGF) and Willebrand factor antigen (vWFAg) and to investigate combinations of allelic variants of the VWF genes in the region -2385T/C and VEGFA in the region -634G/C in menopausal women with NAHS and obesity. Methods. 60 patients, living in Perm, with NAHS and menopausal obesity aged 50.9 ± 1.1 yrs were examined. The control group consisted of 60 healthy, non-obese, menopausal women. By employing enzyme immunoassay (Stat-Fax 2100, USA), the blood concentrations of VEGF were measured using the VEGF-ELISA-BEST kit (ZAO Vector-Best, Novosibirsk) and of vWFAg using the TECHNOZYM vWF:Ag ELISA kit (USA). Single nucleotide polymorphic variants of genes were studied using allele-specific, real time polymerase chain reaction on a CFX-96 detecting amplifier (Bio-Rad Laboratories, Inc., USA) and using the SNP-Screen primers (ZAO Syntol, Moscow). Results. The development of NAHS in obese menopausal women was accompanied by endothelial dysfunction and activation of neoangiogenesis, as indicated by increases in VEGF (p=0.001) and vWFAg (p=0.041). The CC homozygote and the recessive C allele allelic variants of the VEGFA gene (G-634C) were more often detected in the NAHS patients, 21.7% (p=0.04) and 45% (p=0.04), respectively. These values in healthy women were only 8.3% and 33.3%, respectively. Obese women who had recessive homozygotes of CC in the VWF gene (T-2385C) had a 3.04-fold higher probability of developing NAHS, according to the recessive inheritance model. Polymorphism of the VWF gene (T-2385C) was associated with the production of vWFAg (p=0.041). Conclusion. Carrying the C allele of VWF genes in the region -2385T/S and VEGFA in the region -634G/C in the form of the CC genotype may be a risk factor for the development of NAHS in obese women during menopause.