From the Lipid Research Group, Department of Vascular Medicine (M.E.W.,
P.W.A.R., L.F., J.C.D., M.P., J.J.P.K.), and the Department of Medical
Statistics (G.-J.T.), Academic Medical Centre, University of Amsterdam, the
Netherlands, and the Department of Medical Genetics, University of British
Columbia, Vancouver, Canada (S.N.P., M.R.H.).
Correspondence to Michael R. Hayden, Department of Medical Genetics, University of British Columbia, 416-2125 E Mall, Vancouver, BC V6T 1Z4, Canada. E-mail mrh{at}ulam.generes.ca
Background—Recently, a mutation in
the lipoprotein lipase (LPL) gene (N291S) has been reported in 2% to
5% of individuals in western populations and is associated with
increased triglyceride (TG) and reduced HDL
cholesterol (HDLC) concentrations.
Methods and Results—Here we report a significant alteration in
biochemical and clinical phenotype in subjects with familial
hypercholesterolemia (FH) who are heterozygous
for this N291S LPL mutation. Sixty-four FH heterozygotes carrying the
N291S mutation had significantly a higher TG level
(P=.004), a higher ratio of total
cholesterol to HDLC (P<.001), and lower
HDLC concentrations (P=.002) compared with 175 FH
heterozygotes without this LPL mutation. Moreover, the N291S mutation
conferred a significantly greater risk for developing
cardiovascular disease in FH heterozygotes compared
with FH heterozygotes without this LPL mutation (odds ratio, 3.875;
P=.006).
Conclusions—These data provide evidence that a common LPL variant
(N291S) significantly influences the biochemical phenotype and
risk for cardiovascular disease in patients with FH.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
A Common Mutation in the Lipoprotein Lipase Gene (N291S) Alters the Lipoprotein Phenotype and Risk for Cardiovascular Disease in Patients With Familial Hypercholesterolemia
Key Words: genetics • lipoproteins • atherosclerosis
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