CIRCULATING MARKERS FOR BIOSYNTHESIS OF CHOLESTEROL AND BILE-ACIDS ARE NOT DEPRESSED IN ASYMPTOMATIC GALLSTONE SUBJECTS

Background/Aims: Cholesterol gallstone disease is often associated wit h an increased biliary secretion rate of cholesterol, which may be due to abnormalities in hepatic cholesterol metabolism. The aim of the pr esent study was to investigate whether gallstone subjects may have an underlying defect in hepatic cholesterol and bile acid formation. Meth ods: In 41 asymptomatic gallstone subjects, randomly selected from a p opulation of both sexes 40 and 60 years of age, and in 72 age- and sex -matched controls, plasma levels of lathosterol (reflecting hepatic HM G CoA reductase activity) and 7 alpha-hydroxy-4-cholesten-3-one (refle cting cholesterol 7 alpha-hydroxylase activity) were analysed. In a su bgroup of gallstone subjects and controls, plasma levels of 27-hydroxy cholesterol were also determined. Results: The gallstone subjects had normal plasma levels of cholesterol but displayed 20-25% higher plasm a levels of triglycerides compared with the controls. The plasma level of lathosterol was not significantly different between the two groups of subjects whereas the plasma level of 7 alpha-hydroxy-4-cholesten-3 -one was about 40% higher in the gallstone subjects compared with the controls. Positive correlations were obtained between plasma levels of 7 alpha-hydroxy-4-cholestn-3-one and triglycerides in both groups of subjects. The plasma level of 27-hydroxy cholesterol was similar in ga llstone subjects and controls. Conclusions: The previously reported hy persecretion of cholesterol in gallstone patients is not due to a sing le metabolic defect leading to increased hepatic synthesis of choleste rol or decreased catabolism of cholesterol to bile acids via 7 alpha-h ydroxylation or 27-hydroxylation of cholesterol.