Contribution of cholesterol 7α-hydroxylase to the regulation of lipoprotein metabolism

Clinical studies have clearly established a relationship between bile acid synthesis and plasma LDL-cholesterol concentrations. Interruption of the enterohepatic circulation of bile acids leads to increased bile acid synthesis and a reduction in plasma LDL-cholesterol concentrations, New studies indicate that genetic variation in cholesterol 7 alpha-hydroxylase activity accounts for a significant fraction of the inter-individual variation in plasma LDL-cholesterol concentrations in the general population, and a specific CYP7A1 allele associated with increased plasma LDL-cholesterol concentrations has been identified. Studies in which cholesterol 7 alpha-hydroxylase was transiently overexpressed in hamsters and mice indicate that direct manipulation of cholesterol 7 alpha-hydroxylase leads to changes in plasma LDL-cholesterol concentrations. Interestingly, targeted inactivation of the gene encoding cholesterol 7 alpha-hydroxylase does not lead to increased plasma LDL-cholesterol concentrations in mice. Curr Opin Lipidol 10:303-307. (C) 1999 Lippincott Williams & Wilkins.