Relationship between unconjugated hyperbilirubinemia and lipoprotein spectrum

The aim of this study was to analyze the serum bilirubin level, lipid and lipoprotein parameters with the emphasis on the presence of atherogenic small dense LDL in patients with Gilbert's syndrome and to compare these results with probands in the control group. We used a new electrophoretic method, which enables to analyze up to 12 lipoprotein subpopulations. Atherogenic lipoprotein profile is characterized by the presence of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and the presence of small dense LDL lipoproteins. The presence of LDL1 and LDL2 subpopulations, as well as HDL lipoproteins is considered as protective factor.

Molecular - genetic examination of Gilbert\'s syndrome using fragment analysis method was carried out in collaboration with the Centre for Medical Genetics, University Hospital in Bratislava. Total cholesterol and triglycerides in plasma were analyzed from lipid parameters by means of enzymatic CHOD-PAP method, Roche Diagnostics, Germany. Biochemical parameters - bilirubin (total, conjugated and unconjugated), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GMT), (Roche Diagnostics, Germany), TSH, FT3, fT4 (Siemens) were also examined. Serum lipoproteins and their subfractions were examined using Lipoprint LDL System Quantimetrix, CA, USA (12).

We found significantly higher levels of total bilirubin and unconjugated bilirubin in patients with Gilbert's syndrome. In the control group, probands had significantly higher triglycerides levels, VLDL cholesterol levels, IDL cholesterol level, and small dense LDL levels compared to the group with Gilbert\'s syndrome. Probands with Gilbert's syndrome had significantly lower presence of atherogenic lipoprotein spectrum than probands in control group (5% vs. 18%). We found significantly negative correlation between serum unconjugated bilirubin levels and LDL 3-7 (r = - 0.594, p <0.01), as well as between bilirubin and triglycerides (r = -0.540, p<0.01). Serum bilirubin concentration and LDL 1-2 concentration correlated significantly positively (r = 0.451, p <0.05).

The presence of atherogenic lipoprotein spectrum is determined by the particular representation of small dense LDL. Atherogenic spectrum was presented significantly less in patients with Gilbert\'s syndrome compared with the control group (5% vs. 18%). In our study, we have not followed the risk of coronary heart disease or other manifestations of atherosclerotic arteries disability. However, we found the inverse relationship of serum bilirubin levels and atherogenic small dense LDL. We found out that the protective antiatherogenic effect of hyperbilirubinemia is potentiated by low occurence of strongly atherogenic small dense LDL and persons with byperbilirubionemia (in our case represented Gilbert's syndrome), could be protected against the development of atheroscleosis.