(Circulation. 1997;96:1737-1744.)
© 1997 American Heart Association, Inc.
Articles |
Heterozygous Lipoprotein Lipase Deficiency
Frequency in the General Population, Effect on Plasma Lipid Levels, and Risk of Ischemic Heart Disease
From the Department of Clinical Biochemistry, Herlev University Hospital, Herlev (B.G.N., S.A., H.H.W., A.T.-H.); the Copenhagen City Heart Study, Rigshospitalet, National University Hospital (B.G.N., G.J., A.T.-H.); and the Department of Medicine B, Division of Cardiology (R.S.) and Department of Clinical Biochemistry (A.T.-H.), Rigshospitalet, National University Hospital, Copenhagen, Denmark.
Background Patients with mutations on both alleles of the lipoprotein lipase gene resulting in complete lipoprotein lipase deficiency exhibit the chylomicronemia syndrome with severe hypertriglyceridemia and increased risk of pancreatitis and possibly of ischemic heart disease. This study examined frequency, lipid levels, and risk of ischemic heart disease for heterozygous carriers of lipoprotein lipase mutations known to cause the chylomicronemia syndrome in the homozygous state.
Methods and Results Two mutations were screened for in 9259
individuals in a general population sample and in 948 patients with
verified ischemic heart disease. The percent frequencies of
heterozygous individuals with the Gly188
Glu and
Ile194Thr substitutions in the general population were
0.06% (95% CI, 0.04% to 0.23%) and 0% (95% CI, 0.00% to 0.12%),
respectively. The Gly188Glu substitution was associated
with an increase in plasma triglycerides of 0.8±0.3
mmol/L (mean±SEM) and a decrease in plasma HDL
cholesterol, apo A-I, and glucose levels of 0.45±0.07
mmol/L, 17±6 mg/dL, and 1.1±0.2 mmol/L, respectively. On
multiple logistic regression analysis allowing for age, sex,
plasma cholesterol, plasma lipoprotein (a), hypertension,
diabetes mellitus, smoking, and body mass index, both plasma
triglycerides and HDL cholesterol levels were
independent predictors of ischemic heart disease. Finally, the
Gly188Glu substitution was more common among patients
with verified ischemic heart disease (percent frequency of
heterozygous individuals, 0.32%) than among individuals from the
general population (odds ratio, 4.9; 95% CI, 1.2 to 19.6). The effects
of the Gly188Glu substitution were more pronounced than
those of the common Asn291Ser substitution.
Conclusions Heterozygous lipoprotein lipase deficiency due
to the Gly188Glu substitution appears to increase plasma
triglycerides and reduce HDL levels and may thereby
predispose carriers to ischemic heart disease.
Key Words: atherosclerosis • coronary disease • lipoproteins • genes
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