Association of the Pro197Leu polymorphism of the glutathione peroxidase 1 gene and markers of endothelium function in patients with chronic, diffuse liver diseases. Genomic influence on the «clinical phenotype» of chronic, diffuse liver diseases

Abstract

The studies were performed in the group of 28 patients with diffuse liver diseases (CDLD). The clinical liver diseases diagnosis was based on typical parameters. Patient with CDLD frequently present the disturbances of the thyroid homeostasis. Therefore in the group under study this peculiar possibility was also examined. Blood serum level of TSH, free triiodothyronine (fT3), free thyroxine (fT4j were determined in the group under study, followed by the assessment of PR0197LEU polymorphism of the glutathione peroxidase 1 gene (GPXl), level of soluble intercellular adhesion molecule-1 type-ICAM-1, desquamated endothelial cells numbers and the content of the nitrogen monoxide (NO) metabolites in blood serum. In patients with CDLD the reduction of fT3 and the increase offT4 and TSH was not found. PR0197LEU polymorphism of GPX1 gene was associated with the disturbances of the endothelial function as manifested by the higher content of ICAM-1 in the blood serum in homozygotic carriers of the LEU-allele. Perturbations in the endothelial function in patients with CDLD were associated with the polymorphism of PR0197LEU of GPX-1 gene. This phenomenon was also supported by the higher index of the desquamated endothelial cells and lower level of NO in cells of the carriers of LEULEU genotype. In CDLD the abnormal levels of the endothelial cells functional injury markers were associated with respective gene polymorphism of the PRO 197LEU GPX-1 gene. The results of the study revealed the new, genetically determined, mechanism of the liver injury acting within the complex of different, other pathogenetic factors in CDLD.