Bilirubin is a major product of the heme catabolism in the vascular bed with substantial antioxidant properties. These importantly contribute to pathogenesis of diseases associated with increased oxidative stress, including cardiovascular or cancer diseases. In the first part of this PhD project serum bilirubin concentrations were examined in the 1 % representative sample of the general Czech population, together with determination of the prevalence of Gilbert's syndrome. Bilirubin concentrations were determined also within individual polymorphisms of the UGT1A1 gene (OMIM*191740) responsible for bilirubin biotransformation in the liver, including their association with the basic risk factors for atherosclerosis. We also assessed the activity of the standard liver enzymes (representing another significant risk factor for the development of cardiovascular diseases) with surprisingly high proportion of subjects with elevated values. Simultaneously, we determined the concentrations of serum bilirubin in a group of patients with an acute coronary syndrome, who manifested with significantly lower concentrations as compared to general population. In the second part of this research project, the relationship between plasma concentrations of bilirubin and individual variants of UGT1A1 gene polymorphisms...

Inherited disorders of bilirubin metabolism - hereditary hyperbilirubinemias - are metabolic disorders manifested in early childhood. Unconjugated hyperbilirubinemias result from the defect of the enzyme uridine diphosphoglucuronosyltransferase (UGT1A1). UGT1A1 mediates the conjugation of bilirubin with glucuronid acid in hepatocytes and its elimination to water soluble compound. In the next step of bilirubin degradation the transport of conjugated bilirubin from hepatocyte into the bile occure. It is caused by the ATP dependent transporters ABCC2, ATP1B1 and OATP1B3. Mutations in the genes coding the bilirubin transporters results in conjugated hyperbilirubinemia Dubin-Johnson or Rotor syndrome. This study is focused on unconjugated hyperbilirubinemia in adolescents including the non-typical manifestations and the defects of ABCC2 transporter and their phenotype in humans.