Mutations in the Gene for Lipoprotein Lipase

Abstract

Abstract Familial hypercholesterolemia (FH) is characterized by elevated plasma concentrations of LDL cholesterol resulting from mutations in the gene for the LDL receptor. Low HDL cholesterol levels are seen frequently in patients both heterozygous and homozygous for mutations in this gene. Suggested mechanisms for reduced HDL levels in FH patients have been altered apolipoprotein A-1 metabolism and elevated cholesteryl ester transfer protein activity, but the molecular basis for hypoalphalipoproteinemia in any of these patients has not yet been identified. We investigated four large families in which individuals were found to be double heterozygotes for both FH and lipoprotein lipase (LPL) deficiency. These double heterozygotes have significantly less HDL cholesterol than persons with FH or LPL heterozygosity alone. In the double heterozygotes, HDL particle composition is not significantly different from FH heterozygotes, suggesting a quantitative rather than qualitative defect in HDL metabolism in these persons. We propose that mutations in the LPL gene may be a cause of low HDL cholesterol levels in some individuals heterozygous for FH.