© 1995 American Heart Association, Inc.
Articles |
Mutations in the Gene for Lipoprotein Lipase
A Cause for Low HDL Cholesterol Levels in Individuals Heterozygous for Familial Hypercholesterolemia
From the Department of Medical Genetics, University of British Columbia, Vancouver (S.N.P., S.E.G., M.R.H.), and the Lipid Research Centre, Laval University, Ste-Foy, Quebec (C.G., P.J.L., D.G., S.M.), Canada; the University of Utah, Cardiovascular Genetics, Salt Lake City (R.R.W.); the Department of Human Genetics, University of Stellenbosch, Tygerberg, South Africa (M.K.); and the Lipid Research Group, Department of Vascular Medicine, University of Amsterdam (Netherlands) (P.W.A.R., J.C.D., J.J.P.K.).
Correspondence to Dr Michael R. Hayden, Department of Medical Genetics, University of British Columbia, Rm 416-2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada.
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.
Key Words: HDL • lipoprotein lipase • familial hypercholesterolemia
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