doi: 10.1161/hq0202.102919
© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Expression of Type III Hyperlipoproteinemia in Apolipoprotein E2 (Arg158
Cys) Homozygotes Is Associated With Hyperinsulinemia
From the Department of General Internal Medicine (F.d.B., L.M.H., A.H.M.S.), Leiden University Medical Center, and TNO–Prevention and Health (F.d.B., J.A.G.L., L.M.H.), Gaubius Laboratory, Leiden, the Netherlands; the Department of Medicine (A.F.H.S.), Division of General Internal Medicine, University Hospital Nijmegen, Nijmegen, the Netherlands; the Department of Internal Medicine (N.H.), University Hospital Dijkzigt, and Department of Epidemiology and Biostatistics (C.M.v.D.), Erasmus University Medical School, Rotterdam, the Netherlands; and the Department of Vascular Medicine (J.J.P.K.), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Correspondence to Prof Dr L.M. Havekes, TNO–Prevention and Health, Gaubius Laboratory, Zernikedreef 9, 2333 CK Leiden, Netherlands. E-mail LM.Havekes{at}PG.TNO.NL
Type III hyperlipoproteinemia (HLP) is mainly found in homozygous carriers of apolipoprotein E2 (apoE2, Arg158
Cys). Only a small percentage (<5%) of these apoE2 homozygotes develops hyperlipidemia, indicating that additional environmental and genetic factors contribute to the expression of type III HLP. In the present study, first, the prevalence of type III HLP among apoE2 homozygotes was estimated in a Dutch population sample of 8888 participants. Second, 68 normocholesterolemic and 162 hypercholesterolemic apoE2 homozygotes (type III HLP patients) were collected to investigate additional factors influencing type III HLP expression. In the Dutch population sample, apoE2 homozygosity occurred with a frequency of 0.6% (57 of 8888 individuals). Among the 57 E2/2 subjects, 10 type III HLP patients were identified (prevalence 18%). Comparison of normocholesterolemic E2/2 subjects and type III HLP patients showed that the latter had a significantly increased body mass index (25.6±4.0 versus 26.9±3.8 kg/m2, respectively; P=0.03) and prevalence of hyperinsulinemia (26% versus 63%, respectively; P<0.001). Multiple linear regression analysis demonstrated that most of the variability in type III HLP expression can be explained by fasting insulin levels (partial correlation coefficient 
0.50, P<0.001). In contrast to men, apoE2 homozygous women aged 
50 years had significantly higher plasma lipid levels than their counterparts aged <50 years. These data demonstrate that the expression of type III HLP in E2/2 subjects is elicited to a large extent by hyperinsulinemia. In addition, in female apoE2 homozygotes, the expression increases with age; this increase is most likely due to the loss of estrogen production.
Key Words: type III hyperlipoproteinemia • apolipoprotein E • hyperinsulinemia
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